中科院生物化学课件.docx

中科院生物化学课件.docx

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中科院生物化学课件

ChapterTwo

AminoAcidandProtein

UnitOne:

AminoAcid

Aminoacidsarethebuildingblocksofprotein.Twenty-two

aminoacidsareneededtobuildthevariousproteinsusedin

thegrowth,repair,andmaintenanceofbodytissues.

2.1.1.Basicstructureofα-aminoacids

Naturally,aminoacidsinproteinsareallalpha

aminoacids.

COO-

+

H3N

C

H

R

α-aminoacid

Centralα-carbonatom

The22standardaminoacidsdifferonlyinthestructure

ofthesidechainorRgroup.Thesidechainsofthe

aminoacidsdeterminetheirproperties.

2.1.2.Classification（分类）

（1）Hydrophobic（疏水的）,aliphatic（脂肪族）amino

acids－thesidechainsarepoorlysolubleinwater（non-

polar）

O

H2N

CH

CH3

C

OH

H2N

CH

CH

CH3

C

CH3

OH

Alanine

（Ala,A）

丙氨酸

Valine

（Val,V）

缬氨酸

O

O

H2N

CH

CH2

CH

CH3

C

CH3

OH

H2NCHCOH

CHCH3

CH2

CH3

Leucine

（Leu,L）

亮氨酸

Isoleucine

（Ile,I）

异亮氨酸

Thenonpolaraminoacidsarecharacterisedby

havingonlycarbonandhydrogenintheirside

chains.

Theyaregenerallyunreactive,butthefactthatthey

arehydrophobicgivesthemanimportantroletoplay

indeterminingthe3-Dstructureofproteins,asthey

tendtoclusterontheinsideofthemolecule.

Alanine,Valine,LeucineandIsoleucinehave

saturatedhydrocarbonRgroups（i.e.theyonlyhave

hydrogenandcarbonlinkedbysinglecovalent

bonds）.

O

H2N

CH

CH2

CH2

S

CH3

C

OH

Methioninemay

haveantioxidant

activity.Methionine

isanessential

aminoacid.

Methionine

（Met,M）

蛋氨酸

Itssidechain

includesasulfur

atombutremains

hydrophobicin

nature.

L-methioninemayprotect

againstthetoxiceffectsof

hepatotoxins,suchas

acetaminophen（对乙酰氨基酚,

又称扑热息痛）.

脯氨酸

Prolineistheonly

cyclicaminoacid.

Prolinghasnofree

aminogroup,isan

iminoacid（亚氨基酸）.

ThereisnoH-bonddonor

intheprolinepeptidebond.

Thepresenceof

prolineleadstoa

bendorkinkinthe

polypeptidechain.

（2）Hydrophobic（疏水性）,aromatic（芳香族）

aminoacids

O

O

H2N

H2NCHCOH

CH2

HN

Phenylalanine

CH

CH2

C

OH

Trptophane

（Phe,F）

苯丙氨酸

（Trp,W）

色氨酸

PhenylalanineisAlaninewithanextraPhenyl

groupontheend.

Phenylalanineishighlyhydrophobicandisfoundburied

withinglobularproteins.

Phenylalanineisanessentialaminoacid.

TryptophanisalsostructurallyrelatedtoAlanine,

butwithatworing（bicyclic）indole（吲哚）groupadded

inplaceofthesinglearomaticringfoundin

Phenylalanine.

ThepresenceofthenitrogengroupmakesTryptophan

alittlelesshydrophobicthanPhenylalanine.

（3）Polar（极性）,charged（带电荷）aminoacids

O

O

H2NCHCOH

H2NCHCOHH2NCH

CH2

CH2

CH2

CH2

CH2

CH2

HN

CH2

NH

O

COH

N+H

CH2

NH2+

NH3+

NH2

Lysine

Arginine

（Arg,R）

（Lys,K）

精氨酸

赖氨酸

Histidine

（His,H）

组氨酸

Threeaminoacidsarenotonlypolarbutcanalsocarrya

positivechargeandarethereforehighlyhydrophilic（亲水的）.

LysineandArgininebothhavepKaaround10.0andare

thereforealwayspositivelychargedatneutralpH.

ThepKavalueofanorganiccompoundarisesfromtheionizationofeither

anacidorbase,ataspecificcenterinthestructure.

Thedissociation（apparent）constants（Ka）foracidandbaseare

commonlyexpressedas:

wherethecorrespondingequilibriaare:

ThepKaofanacid（orprotonatedbase）issimplyexpressedas:

pKa=-log（Ka）

pKaValuesofAminoAcids

Anaminoacidsuchasglycinecontainstwoionizablegroups:

an〈-carboxylgroupandaprotonated〈-aminogroup.

Asbaseisadded,thesetwogroupsaretitrated.

Titrationofthe〈-Carboxyland〈-AminoGroupsofanAminoAcid.

Histidine,anessentialaminoacid.

AtpH6.5,Histidinecanbe

unchargedorpositivelycharged

dependinguponitslocal

environment.

Theunprotonatedimidazoleis

nucleophilicandcanserveasa

generalbase,whiletheprotonated

formcanserveasageneralacid.

Theabilitytoswitchbetweenthese

twostatescangiveHistidinean

importantroleinthecatalytic

mechanismofenzymesand

explainswhyitisoftenfoundinthe

activesite.

O

O

H2N

H2NCHCOH

CH2

CO

-

O

CH

CH2

CH2

C

O-

C

O

OH

Glutamate

Aspartate

（Glu,E）

（Asp,D）

谷氨酸

天门冬氨酸

Aspartate（Asparticacid）andGlutamate（Glutamicacid）areonly

twoaminoacidswithnegativelycharged（i.e.acidic）sidechains.

IneachcasethepKaofthesidechaincarboxylgroupisabout

4.4,soatneutralpHtheequilibriumiswayoverinfavourofthe

ionisedform.

（4）Polar（极性）,uncharged（不带电荷的）amino

acids

Theseaminoacidspossessoxygen,sulfurand/or

nitrogeninthesidechainandarethereforepolar,

butcannothavetheirRgroupionisedandthusdo

notcarryanoverallcharge.

Thepolarnatureofthesidechainmeansthat

theseaminoacidsreadilyinteractwithwater,i.e.

theyarehydrophilic.

O

O

O

H2NCHCOH

H2NCHCOH

H

CH2

Glycine

OH

（Gly,G）

甘氨酸

Serine

（Ser,S）

丝氨酸

H2N

CH

CH2

OH

Tyrosine

（Tyr,Y）

C

OH

酪氨酸

O

O

H2N

CH

CH2

SH

C

OH

H2NCHCOH

CHOH

CH3

Threonine

（Thr,T）

Cysteine

苏氨酸

半胱氨酸

SerineandThreonineinthecontextofproteinsmaybe

regulatedbyphosphorylation.

Theyarealsoveryimportantintheactivesitesofmany

enzymes.

Cysteine（Cys）isnot

verypolar,andisoften

classifiedasnonpolar.

WhenCysisexposed

toair,itoxidizesto

formCystine,whichis

twocysteinemolecules

joinedbyadisulfide

bond.

Disulfidebondis

importantinthe

formationand

maintenanceofthe

foldedstructurein

manyproteins.

Disulfidebond

Selenocysteine（硒半胱氨酸）,the21staminoacid

Selenocysteinehasastructuresimilartocysteine,but

withanatomofseleniumtakingtheplaceoftheusual

sulfur.Proteinsthatincludeaselenocysteineresidueare

calledselenoproteins.

Selenocysteineincorporationintoselenoproteinsoccurs

co-translationaly.Itisencodedbyaspecificcodon,UGA,

whichintheclassicalcodesignalschaintermination.

O

O

H2N

H2NCHCOH

CH2

CO

NH2

Asparagine

CH

CH

2

CH

2

C

NH

2

C

O

OH

Glutamine

（Asn,N）

天门冬酰胺

（Gln,Q）

谷氨酰胺

Unliketheparentacids,AsparagineandGlutamine

cannotbeionisedandarethereforeuncharged.

Pyrrolysine（吡咯赖氨酸）:

22ndAMINOACID

Science,296,1459and1462（2002）.

Pyrrolysineisanaminoacidusedby

somemethanogenic（organismsthat

producemethane）archaeainenzymes

thatarepartoftheirmethane（甲烷）-

producingmetabolism.

ItiscodedforbyaUAGcodon,whichis

normallyastopcodonbutwhose

meaningmightpossiblybemodifiedby

thepresenceofaspecificdownstream

sequence,namedPYLIS,whichformsa

stem-loopinthemRNA,forcingthe

incorporationofpyrrolysineinsteadof

terminatingtranslation.

2.1.3.AminoAcidChirality（手性）

Almostallα-aminoacidsdisplayaparticulartypeof

stereoisomerismthatcomesfromthemoleculesbeingchiral.

A"chiral"moleculeisonethatisnotsuperimposablewithits

mirrorimage.Likeleftandrighthandsthathaveathumb,

fingersinthesameorder,butaremirrorimagesandnotthe

same.

Chiralityinan〈-aminoacidisduetothe〈-carbonatomin

themoleculebeingjoinedtofourdifferentatomsorgroups.

The〈-carboniscalledthechiralcentre.

Nearlyall〈-aminoacidsinnaturesharethesame

configuration,calledtheL-configuration.Itsmirrorimageis

calledtheD-configuration.

Theabsoluteconfigurationattheα-carbonatomoftheα-

aminoacidsisdesignatedbytheprefixedsmallcapitalletter

DorLtoindicateaformalrelationshiptoD-orL-serineand

thustoD-orL-glyceraldehyde（甘油醛）.

Therelationshipbetweenserineandglyceraldehydemay

thereforeberepresentedas:

2.1.4.Acid-baseproperties（酸碱性质）

ofaminoacid

Theα-COOHandα-NH2groupsinaminoacidsare

capableofionizing（asaretheacidicandbasicR-groups

oftheaminoacids）.

Inaqueoussolution,anH+ionisthereforetransferred

fromoneendofthemoleculetotheothertoforma

zwitterion（兼性离子）.

Thezwitterionisthedominantspeciesinaqueoussolutions

atphysiologicalpH（pH7）.

Thezwitterioncanundergoacid-basereactions,ifweadd

eitherastrongacidorastrongbasetothesolution.

Inthepresenceofastrongacid,the-CO2-endofthis

moleculepicksupanH+iontoformamoleculewithanet

positivecharge.

Theacidicstrength（酸强度）ofthecarboxyl,aminoand

ionizableR-groupsinaminoacidsisdefinedbythe

associationconstant（缔合常数）,Kaormorecommonly

thenegativelogarithm（对数）ofKa,thepKa

Thesymbol"p"meanstakethenegativelogarithmof

whateverfollowsintheformula.forpH,p[anything].

ThepKavalueofanionizablegroupisthepHatwhich

thereareequalamountsofprotonatedandunprotonated

species.

AtapHbelowthepKavalue,agroupwillbemainly

protonated,whileatapHabovethepKa,agroupwillbe

mainlyunprotonated.

Thecarboxylgroupandthe