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CHAPTER 4

PROTEIN STRUCTURE AND FUNCTION


2004 Garland Science Publishin
The Sha!e and S"ruc"ure #$ Pr#"eins
4-1 For each of the following sentences, fill in the blanks with the best word or phrase
selected from the chapter on Protein Structure and Function.
A protein is similar to a charm bracelet that has a linear linked chain or
backbone with charms hanging off at regular intervals. Similar to the
amino acid sequence of a protein, it is the sequence and identity of the
charms that dictate the character of the bracelet. The part of a protein that
is analogous to the bracelet chain is called the
backbone. The parts of a protein that are analogous to the charms are
called the .
4-2 !hich of the following statements is T"#$%
&a' Peptide bonds are the only covalent bonds that can link together two amino acids
in proteins.
&b' The polypeptide backbone is free to rotate about each peptide bond.
&c' (onpolar amino acids tend to be found in the interior of proteins.
&d' The sequence of the atoms in the polypeptide backbone varies between different
proteins.
&e' A protein chain ends in a free amino group at the )*terminus.
%&
4-3 For each of the following sentences, fill in the blanks with the best word or phrase
selected from the list below. (ot all words or phrases will be used+ each word or phrase
should be used only once.
A newly synthesi,ed protein generally folds up into a
conformation. All the information required to
determine a protein-s conformation is contained in its amino acid
. .n heating, a protein molecule will become
due to breakage of bonds.
.n removal of urea, an unfolded protein can become
. The final folded conformation adopted by a
protein is that of energy.
composition irreversible reversible
covalent lowest sequence
denatured noncovalent stable
highest renatured unstable
4-4 Typical folded proteins have a stability ranging from / to 01 kcal2mol at 3/4). Stability
is a measure of the equilibrium between the folded &F' and unfolded &#' forms of the
protein, with the unfolded form having a greater free energy. See Figure 56*6. For a
protein with a stability of /.0 kcal2mol, calculate the fraction of protein that would be
unfolded at equilibrium at 3/4). The equilibrium constant &K
eq
' is related to the free
energy &G4' by the equation7 K
eq
8 09
:G420.6;
Figure 56*6
4-5 <ou wish to produce a human en,yme, protein A, by introducing its gene into bacteria.
The genetically engineered bacteria make large amounts of protein A, but it is in the form
of an insoluble aggregate with no en,ymatic activity. !hich of the following procedures
might help you to obtain soluble, en,ymatically active protein% $=plain your reasoning.
A. >ake the bacteria synthesi,e protein A at a slower rate and in smaller amounts.
?. @issolve the protein aggregate in urea, then dilute the solution and gradually
remove the urea.
). Treat the insoluble aggregate with a protease.
@. >ake the bacteria overproduce chaperone proteins in addition to protein A.
$. Aeat the protein aggregate to denature all proteins, then cool the mi=ture.
%2
4-6 !hich of the following statements about proteins is T"#$%
&a' The three*dimensional structure of a protein can usually be predicted from
knowledge of its amino acid sequence.
&b' Two proteins having similar amino acid sequences will often have similar shapes.
&c' Proteins containing fewer than 099 amino acids cannot fold into stable structures.
&d' >ost proteins contain more than ;999 amino acids.
&e' The detailed three*dimensional structure of a protein can usually be determined
by electron microscopy.
4-7 The heli= and sheet are found in many different proteins because they are formed by
&a' hydrogen bonding between the amino acid side chains most commonly found in
proteins.
&b' noncovalent interactions between amino acid side chains and the polypeptide
backbone.
&c' ionic interactions between charged amino acid side chains.
&d' hydrogen bonding between atoms of the polypeptide backbone.
&e' hydrophobic interactions between the many nonpolar amino acids.
4-8 A. Bn the schematic diagram of a protein given in Figure 56*C, label the three protein
strands that are linked together in a sheet with a DbE.
Figure 56*C
?. Bs this sheet parallel or antiparallel%
%'
4-9 For each polypeptide sequence listed, choose from the options given below to indicate
which secondary structure the sequence is most likely to form upon folding. The
nonpolar amino acids are italici,ed.
A. Leu*gly*val*leu*ser*leu*phe*ser*gly*leu*met*trp*phe*phe*trp*ile
?. Leu*leu*gln*ser*ile*ala*ser*val*leu*gln*ser*leu-leu*cys*ala*ile
). Thr*leu*asn*ile*ser*phe*gln*met*glu*leu*asp*val*ser*ile*arg*trp
amphipathic heli= hydrophilic heli= hydrophobic heli=
amphipathic sheet hydrophilic sheet
4-10 A helical structure
&a' will contain two, three, four, or some other e=act number of subunits per each turn
of the heli=.
&b' that is right*handed if viewed from one end will appear to be left*handed if
viewed from its other end.
&c' can form only by Foining together a string of identical protein molecules.
&d' can form either within a single large molecule or from an assembly of separate
molecules.
&e' is usually maintained entirely by covalent bonds.
4-11 @rawn below are segments of sheets, which are rigid pleated structures held together
by hydrogen bonds between the peptide backbones of adFacent strands &Figure 56*00'.
The amino acid side chains attached to the )

carbons are omitted for clarity.


Figure 56*00
A. Bndicate whether each structure is parallel or antiparallel.
?. @raw the hydrogen bonds as dashed lines &* * * * * *'.
%4
4-12 For each of the following sentences, fill in the blanks with the best word or phrase
selected from the list below. (ot all words or phrases will be used+ each word or phrase
should be used only once.
The helices and sheets are e=amples of protein
structure. A protein such as hemoglobin, which is composed of more than
one protein , has structure. A
protein-s amino acid sequence is known as its
structure. A protein is the modular unit from which
many larger single*chain proteins are constructed. The three*dimensional
conformation of a protein is its structure.
allosteric ligand secondary
domain primary subunit
heli= quaternary tertiary
4-13 <ou are digesting a protein G;1 amino acids long with the en,ymes Factor Ha and
thrombin, which are proteases that bind to and cut proteins at particular short sequences
of amino acids. <ou know the amino acid sequence of the protein and so can draw a map
of where factor Ha and thrombin should cut it &Figure 56*03'. <ou find, however, that
treatment with each of these proteases for an hour results in only partial digestion of the
protein, as summari,ed under the figure. Iist the segments &A:$' of the protein that are
most likely to be folded into compact, stable domains.
Figure 56*03
4-14 )alculate how many different amino acid sequences there are for a polypeptide chain 09
amino acids long.
4-15 All known proteins in cells adopt a single stable conformation because
&a' any chain of amino acids can fold up into only one stable conformation.
&b' protein chains that can adopt several different conformations have been weeded
out by natural selection.
&c' chaperone proteins prevent the protein from adopting a preferred unstable
conformation.
&d' they are comple=ed with other molecules that keep them in that one particular
conformation.
&e' one conformation always has the most positive free energy.
%%
4-16 A friend tells you that she has Fust discovered that the protein responsible for causing
dogs to chase cars is a member of the >AP protein kinase family. Bn response to your
blank stare, she adds that the yeast protein Fus3p, which is involved in response to a yeast
hormone is also a >AP kinase family member. Although you still have no idea of what
either a >AP kinase or Fus3p is, which one or more of the following statement&s' can
you safely predict to be T"#$% $=plain your reasoning.
&a' The dog protein and Fus3p have mostly similar amino acid sequences.
&b' The dog protein and Fus3p cataly,e the transfer of a phosphate group to another
molecule.
&c' The dog protein phosphorylates the same type of molecule that Fus3p
phosphorylates.
&d' The dog protein and Fus3p have identical three*dimensional structures.
&e' The dog protein is involved in response to hormones.
4-17 A hemoglobin molecule
&a' is composed of four protein domains.
&b' is a dimer of polypeptide chains.
&c' has two binding sites for nitrogen gas.
&d' is composed of two different types of protein subunits.
&e' is composed of four identical protein subunits.
4-18 !hen purified samples of protein < and a mutant version of protein < are both washed
through the same gel*filtration column, mutant protein < runs through the column much
slower than the normal protein. !hich one or more of the following changes in the
mutant protein is2are most likely to e=plain this result%
&a' The loss of a binding site on the mutant protein surface through which protein <
normally forms dimers
&b' A change that results in the mutant protein acquiring an overall positive instead of
a negative charge
&c' A change that results in mutant protein < being larger than the normal protein
&d' A change that results in mutant protein < having a slightly different shape from
the normal protein
&e' The loss of a binding crevice in the mutant protein < for a small molecule ligand
4-19 $=amine the three protein monomers in Figure 56*0J. From the arrangement of
complementary binding surfaces, which are indicated by similarly shaped protrusions and
invaginations, decide whether each monomer could assemble into a defined multimer, a
filament, or a sheet.
Figure 56*0J
%(
4-20 For each of the following indicate whether the individual folded polypeptide chain forms
a globular &K' or fibrous &F' protein molecule.
A. Leratin
?. Iyso,yme
). $lastin
@. )ollagen
$. Aemoglobin
F. Actin
4-21 S:S bonds
&a' are formed by the cross*linking of methionine residues.
&b' are formed mainly in proteins that are retained within the cytosol.
&c' stabili,e but do not change a protein-s final conformation.
&d' can be broken by o=idation through agents such as mercaptoethanol.
&e' rarely form in e=tracellular proteins.
H#) Pr#"eins *#r+
4-22 !hich of the following statements is FAIS$%
&a' The three dimensional structure of a protein dictates its function by determining
its binding specificity for other molecules.
&b' >any proteins have more than one binding site.
&c' ?inding between protein and ligand generally involves noncovalent bonds.
&d' Proteins are designed to bind their ligands as tightly as possible.
&e' )hanges in the amino acid sequence of a protein can decrease binding to a ligand,
even if the altered amino acid does not lie in the binding site for the ligand.
4-23 For each of the following sentences, fill in the blanks with the best word or phrase
selected from the list below. (ot all words or phrases will be used+ each word or phrase
should be used only once.
The human immune system produces of different
immunoglobulins, also called , which enable the
immune system to recogni,e and fight germs by specifically binding one
or a few related . The hypervariable structural
element that forms the ligand binding site is comprised of several
. Purified antibodies are useful for a variety of
e=perimental purposes, including protein purification using
chromatography.
affinity billions ligands
antibodies coiled coils loops
antigens hundreds si,e e=clusion
strands ion e=change
%,
4-24 For each functional class of en,ymes in Iist 0, choose the kind of reaction it cataly,es
from Iist ;. #se each item in Iist ; no more than once.
List 1
A. Linase
?. Phosphatase
). Polymerase
@. Aydrolase
$. @ehydrogenase
F. ATPase
K. Synthase
A. Protease
List 2
0. .=idation of substrate
;. "eduction of substrate
3. Addition of phosphate group
6. "emoval of phosphate group
1. )leavage of substrate using water
G. )ondensation reaction in anabolic pathway
/. "epeated condensation reactions with similar
building blocks to form a growing chain
C. Aydrolysis of nucleotide triphosphate
J. Aydrolysis of peptide bonds
4-25 For each of the following sentences, fill in the blanks with the best word or phrase
selected from the list below. (ot all words or phrases will be used+ each word or phrase
should be used only once.
Any substance that will bind to a protein is known as its
. $n,ymes bind their at the
. The en,yme he=okinase is so specific that it reacts
with only one of the two of glucose. $n,ymes
cataly,e a chemical reaction by lowering the ,
because they provide conditions favorable for the formation of a
intermediate called the .
.nce the reaction is completed, the en,yme releases the
of the reaction.
activation energy inhibitors products
active site isomers substrates
free energy ligand transition state
high*energy low*energy
4-26 .ne way that an en,yme can lower the activation energy required for a reaction is to bind
the substrate&s' and distort its structure so that the substrate more closely resembles the
transition state of the reaction. This mechanism will be facilitated if the shape and
chemical properties of the en,yme-s active site are more complementary to the transition
state than to the undistorted substrate, in other words, if the en,yme were to have higher
affinity for the transition state than for the substrate. Lnowing this, your friend looked in
an organic chemistry te=tbook to identify a stable chemical that closely resembles the
transition state of a reaction that converts H into <. She generated an antibody against
this transition state analog and mi=ed the antibody with chemical H. !hat do you think
might happen%
%-
4-27 !hich of the following statements is FAIS$%
&a' Polypeptide chains are never covalently linked to lipids or sugars.
&b' >ost vitamins bind noncovalently to the active sites of particular en,ymes and
provide essential catalytic assistance.
&c' Some catalytic functions would be difficult or impossible using only the
chemistry offered by the ;9 amino acid side chains.
&d' Small molecules tightly bound to en,ymes can form transient bonds during
catalysis.
&e' Proteins that interact with photons and gas molecules often do so by virtue of
tightly bound small molecules.
H#) Pr#"eins Are C#n"r#lled
4-28 The biosynthetic pathway for the two amino acids $ and A is shown schematically in
Figure 56*;C. <ou are able to show that $ inhibits en,yme M, and A inhibits en,yme H.
$n,yme T is most likely to be subFect to feedback inhibition by
alone.
Figure 56*;C
&a' A
&b' ?
&c' )
&d' $
&e' A
4-29 Bn general, a ligand that binds to only one conformation of an allosteric protein will
stabili,e the bound conformation. .=ygen binds to the Do=yE conformation of
hemoglobin, while carbon dio=ide and the small organic molecule ?PK bind to the
Ddeo=yE conformation, each at different sites. !hich of the following statements is
FAIS$%
&a' A high concentration of carbon dio=ide will stimulate binding of ?PK to
hemoglobin.
&b' A high concentration of o=ygen will stimulate dissociation of ?PK and carbon
dio=ide from hemoglobin.
&c' A high concentration of carbon dio=ide will cause o=ygen to dissociate.
&d' Bn the presence of ?PK, a lower concentration of carbon dio=ide is required to
cause dissociation of o=ygen.
&e' A variant of hemoglobin that has a lower affinity for ?PK will bind to o=ygen less
tightly than normal hemoglobin in the presence of the same level of ?PK.
%.
4-30 The movement of a ciliated proto,oan is controlled by a protein called "acerH. !hen this
protein binds to another protein found at the base of the cilia, it stimulates the cila to beat
faster and the proto,oan to swim faster. This ciliar protein, Speed, can be phosphorylated
and can only bind to "acerH in its phosphorylated form. <ou have identified the
threonine residue at which Speed is phosphorylated and changed it to an alanine residue.
Aow would you e=pect the mutant proto,oan to behave%
&a' Swims fast occasionally
&b' Always swims fast
&c' (ever swims fast
&d' Switches rapidly back and forth between fast and slow swimming
&e' )annot move at all
4-31 !hich of the following mutant proto,oa would swim fast all of the time%
&a' .ne lacking the protein kinase that phosphorylates the Speed protein
&b' .ne lacking the Speed protein
&c' .ne lacking the "acerH protein
&d' .ne in which the protein phosphatase that dephosphorylates the Speed protein is
produced in much greater amounts than normal
&e' .ne lacking the protein phosphatase
4-32 Some of the en,ymes that o=idi,e sugars to yield useable cellular energy &for e=ample,
ATP' are regulated by phosphorylation. For these en,ymes, would you e=pect the
inactive form to be the phosphorylated form or the dephosphorylated form% $=plain your
answer.
4-33 KTP*binding proteins
&a' form a transient covalent bond with guanine nucleotides.
&b' are generally activated by factors that increase their rate of KTP hydrolysis.
&c' immediately release the K@P produced by KTP hydrolysis.
&d' DresetE themselves by phosphorylating bound K@P.
&e' do not readily e=change bound K@P for KTP unless stimulated to do so.
4-34 The "as protein is a KTPase that functions in many growth*factor signaling pathways. Bn
its active form, with KTP bound, it transmits a downstream signal that leads to cell
proliferation+ in its inactive form, with K@P bound, the signal is not transmitted.
>utations in the gene for "as are found in many cancers. .f the choices below, which
alteration of "as activity is most likely to contribute to the uncontrolled growth of cancer
cells%
&a' A change that prevents "as from being made.
&b' A change that increases the affinity of "as for K@P.
&c' A change that decreases the affinity of "as for KTP.
&d' A change that decreases the affinity of "as for its downstream targets.
&e' A change that decreases the rate of hydrolysis of KTP by "as.
(0
4-35 A molecule of the motor protein !innebago, supplied with ATP, is moving along a
microtubule in the direction shown in Figure 56*31.
Figure 56*31
!hat will happen if you suddenly remove all ATP from the system by adding an en,yme
that hydroly,es ATP%
&a' (o change7 !innebago will continue to move from point A to point ?.
&b' !innebago will wander back and forth along the microtubule.
&c' !innebago will move backwards &towards point A instead of point ?'.
&d' !innebago will stall on the microtubule.
&e' !innebago will continue to move from point A to point ?, but at a slower rate.
4-36 Assembling the individual en,ymes required for a multistep process into a protein
machine is likely to increase the efficiency with which the entire process is carried out in
all of the following ways $H)$PT by
&a' increasing the rate at which the individual en,ymes encounter their substrates.
&b' ordering the reactions sequentially.
&c' increasing the V
ma=
of the individual en,ymes.
&d' coordinating the regulation of the individual en,ymes.
&e' coordinating the movement of the en,ymes.
4.37 $=plain how new proteomic approaches may advance the goal of being able to predict the
three*dimensional structure of a protein from its amino acid sequence. !hy is this an
important goal%
(&
Ans)ers
4-1 A protein is similar to a charm bracelet that has a linear linked chain or backbone with charms
hanging off at regular intervals. Similar to the amino acid sequence of a protein, it is the
sequence and identity of the charms that dictate the character of the bracelet. The part of a
protein that is analogous to the bracelet chain is called the polypeptide backbone. The parts
of a protein that are analogous to the charms are called the side chains.
4-2 )hoice &c' is the answer. )hoice &a' is untrue, as some proteins also contain covalent
disulfide bonds &:S:S: bonds' linking two amino acids. )hoice &b' is untrue, as the
peptide bond is rigid. )hoice &d' is untrue, as the sequence of atoms in the polypeptide
backbone itself is always the same from protein to protein+ it is the order of the amino
acid side chains that differs. )hoice &e' is untrue, as a protein chain has a carbo=yl group
at its )*terminus.
4-3 A newly synthesi,ed protein generally folds up into a stable conformation. All the
information required to determine a protein-s conformation is contained in its amino acid
sequence. .n heating, a protein molecule will become denatured due to breakage of
noncoalent bonds. .n removal of urea, an unfolded protein can become renatured.
The final folded conformation adopted by a protein is that of lo!est energy.
4-4 The G4 of the unfolding reaction is equal to the stability of the protein, /.0 kcal2mol. At
equilibrium, the ratio of unfolded to folded protein is
K
eq
8 N#O2NFO 8 09
:G420.6;
8 09
:/.020.6;
8 09
:1
.
Thus, one molecule in 099,999 is unfolded.
(2
4-5 )hoices A, ?, and @are all worth trying. Some proteins require molecular chaperones in
order to fold properly within the environment of the cell. Bn the absence of chaperones, a
partly folded polypeptide chain has e=posed amino acids that can form noncovalent
bonds with other regions of the protein itself and with other proteins, thus causing
nonspecific aggregation of proteins.
A. Since the protein you are e=pressing in bacteria is being made in large quantities,
it is possible that there are not enough chaperone molecules in the bacterium to
fold the protein. $=pressing the protein slowly and at lower levels might increase
the amount of properly folded protein.
?. "emoving the urea slowly and gradually often allows the protein to refold.
Presumably, under less crowded conditions, the protein should be able to refold
into its proper conformation.
). Treating the aggregate with a protease, which cleaves peptide bonds, will probably
solubili,e the protein by trimming it into pieces that do not interact as strongly with
one another+ however, chopping up the protein will also destroy its en,ymatic activity.
@. .vere=pressing chaperone proteins might increase the amount of properly folded
protein. #rea should solubili,e the protein and completely unfold it.
$. Aeating can lead to the partial denaturation and aggregation of proteins to form a
solid gelatinous mass, as when cooking an egg white, and rarely helps solubili,e
proteins.
4-6 &b' Since a protein-s three*dimensional structure is determined by its amino acid
sequence, proteins with similar amino acid sequences will often have very similar
shapes.
4-7 &d'
4-8 A. See Figure A6*C.
Figure A6*C
?. Antiparallel
('
4-9 A. Aydrophobic heli=. (early all of the amino acid side chains in this sequence
are nonpolar or hydrophobic, which favors the only hydrophobic option given in
the list.
?. Amphipathic heli=. Bn an ideal heli=, there are 3.G residues per complete
turn. Thus, an amphipathic heli= with one hydrophobic side and one hydrophilic
side will have, minimally, nonpolar side chains &(' repeating every third then ne=t
fourth amino acid7 (==(===(==(===(. Polar side chains &P' will e=hibit the
same pattern, but shifted relative to the nonpolar side chains7 for e=ample,
==P===P==P===P==P.
). Amphipathic sheet. @ue to the ,ig*,ag like structure of a sheet, a sequence
with alternating nonpolar and polar side chains may form an amphipathic sheet
that is hydrophobic on one side and hydrophilic on the other.
4-10 &d'
4-11 A. &A' is parallel and &?' is antiparallel
?. See Figure A6*00.
Figure A6*00
4-12 The helices and sheets are e=amples of protein secondary structure. A protein such
as hemoglobin, which is composed of more than one protein subunit, has quaternary
structure. A protein-s amino acid sequence is known as its pri"ary structure. A protein
do"ain is the modular unit from which many larger single*chain proteins are
constructed. The three*dimensional conformation of a protein is its tertiary structure.
(4
4-13 Segments ? and @. To cut the protein chain, Factor Ha and thrombin must bind to their
preferred cutting sites. Bf these sites are folded into the interior of a stable protein domain,
it will be much more difficult for the proteases to gain access to them than if they are part
of a relatively unstructured part of the chain. Aence, sites that are folded inside of a
protein domain are protected from cleavage by a protease. From the si,es of the
fragments produced by digestion of the protein with Factor Ha, we can conclude that the
en,yme does not cut at the sites in regions ? or @, although it does cut in region $. From
the si,es of the fragments produced by thrombin, we can conclude that this en,yme cuts
at the sites in A, ), and $. Therefore, the segments of the protein that are most likely to
be folded into compact stable domains are ? and @.
4-14 The quantity ;9
09
8 appro=imately 09
03
.
4-15 &b'
4-16 )hoices &a' and &b' are the answers. >embers of the same protein family have similar
protein sequences, similar three*dimensional structures, and roughly similar chemical
activities &for e=ample, all of the serine proteases cataly,e the cleavage of a peptide
bond'. So if the dog protein is a >AP protein kinase, it is similar in sequence to other
>AP kinases &choice &a'' and most likely has kinase activity &the transfer of a phosphate
group from ATP to another molecule' &choice &b''. Aowever, the actual substrates and the
physiological function of proteins in the same family can differ quite markedly, so it is
unlikely that the dog protein phosphorylates the same type of molecule that Fus3p does or
is involved in the same type of response that Fus3p mediates.
4-17 &d'
4-18 )hoice &a' is the answer. @imers formed by a normal protein will run through the gel*
filtration column faster than a mutant protein < monomer. )hoices &b' and &e' are
unlikely, as gel*filtration columns separate proteins on the basis of si,e, not charge or
affinity for small molecules. )hoice &c' is unlikely, since if the mutant protein were
larger than normal it would be less able to enter the porous beads and would run through
the column at a faster speed than the normal protein. )hoice &d' is unlikely, since a small
change in shape without a change in si,e would be unlikely to have a maFor effect on the
behavior of a protein in gel*filtration column.
4-19 A. @efined multimer with four subunits, called a tetramer.
?. Sheet
). Filament
4-20 APF+ ?PK+ )PF+ @PF+ $PK+ FPK
4-21 )hoice &c' is the answer. )hoice &a' is incorrect since S:S bonds are formed between
cysteines. )hoice &b' is incorrect, as they are formed mainly in e=tracellular proteins.
)hoice &d' is incorrect+ they are broken by mercaptoethanol, but by reduction not
o=idation. )hoice &e' is incorrect for the reason stated in choice &b'.
(%
4-22 &d' False. >ost proteins need to release their ligand at some point. For e=ample,
hemoglobin would be useless as a carrier of o=ygen if it never released the
o=ygen to the tissues that need it. Bn addition, en,ymes could not be catalysts if
they did not release the product after its formation from substrate.
4-23 The human immune system produces billions of different immunoglobulins, also called
antibodies, which enable the immune system to recogni,e and fight germs by
specifically binding one or a few related anti#ens. The hypervariable structural element
that forms the ligand binding site is comprised of several loops. Purified antibodies are
useful for a variety of e=perimental purposes, including protein purification using a$$inity
chromatography.
4-24 AP3+ ?P6+ )P/+ @P1+ $P0+ FPC+ KPG+ APJ
4-25 Any substance that will bind to a protein is known as its li#and. $n,ymes bind their
substrates &or inhibitors' at the actie site. The en,yme he=okinase is so specific that it
reacts with only one of the two iso"ers of glucose. $n,ymes cataly,e a chemical
reaction by lowering the actiation ener#y, because they provide conditions favorable
for the formation of a hi#h-ener#y intermediate called the transition state. .nce the
reaction is completed, the en,yme releases the products of the reaction.
4-26 Bf your friend was lucky, she made a Dcatalytic antibodyE that cataly,ed the conversion of
H into <. Such catalytic antibodies have been isolated and shown to cataly,e a variety of
reactions, but with lower efficiency than genuine en,ymes.
4-27 &a'
4-28 &c' Bf $ alone inhibited T, then it would be possible to shut down the pathway even if
A were in low abundance. Iikewise, if A alone inhibited T, it would be possible
to shut down the pathway even if $ were in low abundance. An en,yme is
generally not inhibited by its substrate. Ievels of ) will build up only if both $
and A are abundant and have inhibited M and H. Bt is more likely that ) alone
rather than ? alone will inhibit T, since ? will accumulate only after ) has done
so.
4-29 &e' Since carbon dio=ide and ?PK stabili,e the form of hemoglobin that o=ygen
cannot bind to, either ?PK or carbon dio=ide will stimulate the dissociation of
o=ygen+ likewise, a high concentration of o=ygen will stimulate the dissociation
of carbon dio=ide and ?PK. Since ?PK and carbon dio=ide both bind to and
stabili,e the same form of hemoglobin, these two ligands should help each other
bind. Since ?PK binding stimulates the dissociation of o=ygen, a variant of
hemoglobin that does not bind ?PK well should bind more tightly to o=ygen.
((
4-30 &c' The alanine side chain has no hydro=yl &.A' group and therefore cannot be
phosphorylated. ?ecause the altered Speed protein cannot be phosphorylated, it
can never bind "acerH. !hen "acerH is not bound to Speed, the cilia beat more
slowly and thus the mutant proto,oan would never swim fast.

4-31 )hoice &e' is the answer. The lack of the protein phosphatase would mean that the Speed
protein could remain phosphorylated all the time, causing the organism to swim fast. A
mutant missing "acerH &choice &c'' would not be able to swim fast at all and neither
would one missing the protein kinase that phosphorylates Speed &choice &a'' or one
lacking the Speed protein &choice &b''. .ne that overproduced the protein phosphatase
&choice &d'' would keep the Speed protein permanently dephosphorylated and thus would
also be unable to swim fast.
4-32 Bn general the inactive form is the phosphorylated form. The main purpose of glycolysis
and the citric acid cycle is to generate ATP+ thus the en,ymes are inactive when ATP is
high and active when ATP is low. Bt makes sense that cells would not want to have to
phosphorylate their en,ymes to turn them on when ATP levels are already low, since
phosphorylation requires ATP.
4-33 )hoice &e' is the answer. KTP*binding proteins generally hydroly,e KTP and then retain
the bound K@P until stimulated to e=change K@P for KTP by some other protein. The
conformational change driven by hydrolysis, therefore, is due to the loss of a single
phosphate group, not the whole guanine nucleotide &choice &c''. K proteins do not form
covalent intermediates with either KTP or K@P &choice &a''. Since the KTP*bound form
is usually the active form, a factor that stimulates hydrolysis will inhibit the protein
&choice &b''. K proteins are reset by nucleotide e=change, not by rephosphorylation of
bound K@P &choice &d''.
4-34 &e' This choice will increase the amount of "as that is in the KTP*bound state and
thus increase the strength of the proliferative signal. All of the other changes will
decrease the strength of the proliferative signal sent through the pathway by "as.
4-35 &d' >otor proteins that are capable of unidirectional movement require ATP &or KTP'
hydrolysis to drive them in one direction. This is because the conformational
change is coupled to ATP hydrolysis, such that movement in the reverse direction
requires ATP synthesis. Aence, if ATP is depleted, the protein will completely stop
moving, being unable to move forward for lack of ATP and unable to move
backward because ATP synthesis is thermodynamically unfavorable.
(,
4-36 &c' Bf the product of one en,yme is the substrate for another, assembling the en,ymes
into a machine will bring the en,ymes closer to their substrates because the
product will have to diffuse only a short distance to the ne=t en,yme. Bf the
en,ymes are properly arranged spatially, one can easily imagine how the machine
could also facilitate the ordering of reactions. Kathering the en,ymes into a
comple= also makes it easier to regulate and move all of the en,ymes together. A
machine is only as good as each of its parts, however, and if an en,yme has a low
turnover number, comple=ing it with other proteins is unlikely to increase the
en,yme-s ability to convert substrate into product.
4-37 Bt is hoped that large*scale analyses of many protein structures simultaneously will
quickly complete the list of all protein folding patterns and all protein domains that
evolved in living organisms. The identification of the thousands of different protein folds
Pthe structural units that form the basis of all proteinsPmay allow elucidation of the
rules that determine the conformation adopted by each amino acid sequence. Then, when
a scientist identifies a protein responsible for a particular disease or discovers a protein in
a new organism, it will be immediately possible to hypothesi,e its structure and thus its
function.
(-