Proteins and Molecular Mechanisms
Proteins and Molecular Mechanisms BCH 455
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Date Created: 10/15/15
Proteins They are a relatively homogeneous class of molecules All are the same type of linear polymer built of various combinations of the same 20 amino acids differing only in the sequence Their functional diversity lies in the threedimensional structures that these linear polymers can make by simply being linked in different sequences What do proteins do Pretty much everything Store and transport a variety of molecules Guide flow of electrons in processes such as photosynthesis Transmit information between specific cells within an organ Control passage of molecules across membranes of compartmentalized cells and organelles Function in immune system to defend against intruders antibodies Control gene expression by binding to specific sequences of nucleic acids to turn them onoff Structural stability within cells including hair nails tendons and bones of animals 19 Amino Acids have this structure Onhthe Rgroup changes A ways the Lisomer Exception PrOHne mm CH Mac CH CH Amer 5mquot Nuckeuphlllc OH H L HQNXCOOH HZN coon HQN COOH Glycmz G y G Alanine Na A Senna Sen 5 MW 5705 MW7109 MW 6705 pKa 15 Hydrophobic Hgnjfcoon HEN600H HQN COOH Vallne Val v Leucme Leu L lsnleumne quot5 n 3 MWna1e Arumalm H CH N 1 HEN COGH HEN coon Phenyla anrne1PheF Tymsme Ty w Tryplophanr p W Mw 14715 Mw 153 MW 3621 Amide Ham 0 o NHZ HN NHf NH2 H2N COOH HZN cooH HEN CDOH Aspayagme Asn N Glmzmme Gm m sthdme st H Mwmn MW212EJA MW11374 pKaEuA IOH HZN cooH Thleomne Th MW mux pK LT ans M 31 Acidic 0 0H HZN COOH Aspamc Am up up MW 11509 pKa 9 my HZN Lysine Lys Mw 12317 pKa cooH K 1079 SH 1 HEN COUH Cysteine Cys cp MW39 1031541 525 CL N H COOH Pyullne1PmP MW 9712 HEN CODH 6mm AcIdKSlu 9 MW 12912 pKz 407 HEN YNHQquot NH HZN cooH Avgmme Ayg R MW115619 pKa12AE In proteins the amino acid is linked together by PEPTIDE BONDS Peptide bend Each amino acid in a polypeptide chain is referred to as a residue Usually between 50 to 3000 linked together to form a polypeptide chain gt 50 protein lt50 polypeptide This polymeric linear linkage Primary seguence structure The sequence of amino acids in a proteinpolypeptide chain generally identifies a protein unambiguously Peptide bond appears to have 40 double bond character which makes it strong Rotation about this bond is restricted and pretty planar Trans Conformer Asymmetric center Shorter bonds are stronger and have less movement Cis Conformer 1 4 This conformation is not very well liked except with proline 2 Cis conformations tend to C create steric hindrance and repulsions with the side H H chains of the amino acids R groups All about energy Trans is favored energetically fewer repulsions However if the residue that follows a peptide bond is a proline its cyclic side chain diminishes the repulsive effects and Cis trans isomers are approximately the same energetically maybe around a factor of 4 difference rather than 1000 This could cause problems from a structural analysis viewpoint example D9K Resonance of the peptide bond tend to redistribute its electrons and the polypeptide backbone is correspondingly polar The H and N atoms appear respectively to have positive and negative charges of 020 electrons whereas C and 0 respectively have positive and negative charges of 042 electron The positive and negative charges help to give the protein its functionality This gives the peptide bond a permanent dipole moment of 35 Debye units The peptide backbone of each residue contains one potent hydrogen bond donor NH and a hydrogen bond acceptor CO this is critical for the 3D architecture of proteins The peptide backbone is not very reactive chemically The only groups usually ionized are the terminal or amino and carboxyl groups which normally have pKa values of about 74 to 39 respectively depending on the nature of the terminal amino acid residue A proton is added or lost to internal peptide bonds only at extremes of pH The apparent pK value of the amide NH for deprotonation is between 15 and 18 and is in the region of 8 to 12 for protonation The oxygen atom of the carbonyl group is protonated more readily with an apparent pK of about 1 These properties facilitate the exchange of hydrogen isotopes between the backbone and aqueous solvents which is important to the study of protein fluctuations in solution The amide proton has the ability to exchange with the solution to create a constant exchange process Glycine Ul l It has no ClC asymmetry Glycine is a very flexible residue because there is no steric hindrance This allows glycine to be dynamic It is very common in loops Aliphatics Ma tiff Hydrophobic They hate water but love each other They also like other nonpolar atoms They are referred to as STICKY They help stabilize the folded conformations of proteins Cyclic imino residue Rigid aboulthe NrE C bond Slightly puckered with gammar HZCCEIZ Carbon raised a little I no ami e rolequot can not I C 2 f d p HN huc hydrogen bond H CQOH The peptide bond before a proline likes to be cis proline Hydroxyl groups The OH loves to Hydrogen bond can act as a switch in catalysis Acidic residues Even though they look similar the are not close functionally due to the extra CH2 on Glutamine The COO group clearly likes positive charges which makes these good for metal ion binding Proteins do whatever necessary to dispel charge such as binding to metals Amide Residues Neither is too reactive Have polar ends and are H bond acceptors and donors eg If an Asn and Gly are next to each other a kink could possibly form due to deamidation side chain and backbone reactwhy Gly Basic Residues E E E E E HzN lIS coon H lysine Normally ionized but if not the side chain becomes very reactive and a potent nucleophile Good Hbond donor Tend to be hydrophobic within chain and very nonhydrophobic at end of chain Interact with DNA nucleic acids af l 1 arma m 0001 g L Has a very long side chain which likes to interact with water in solution because end is polar Searches for negative species mostly on surface of proteins Imidazole ring 1 an H 51 CH Hw coon H Tertiary arnine Good nucieophiie donates eiectronsi In its nonionized form the nitrogen with the hydrogen is an eiectrophiie and donorfor Hbonding The other nitrogen is a nucieophiie and acceptor for hydrogen bonding Very versatiie side ofthe residue The 2 N s within the ring are denoted 5 and 52 Two tautorners can exist the protonated one Metals Aromatics The largest and most fluorescent sidechain Occurs least frequently 0 112 HzN lf COOH H phenylalanine Th e r i n g ca n reorient Flipswitch 0H HW JIJ COOH H tyrein The OH group makes it quite reactive Can hydrogen bond Molar absorptivilyl a 40000 20000 10000 5000 2000 1000 llllllll ilililll lililllll l l 200 l 200 250 Wavelength lnml 320 The aromatic residues are responsible for ultraviolet and fluorescence properties of proteins also known as chromophores The spectral properties of the side chains are very sensitive to local environmental changes and are useful probes of structures Sulfur containing residues 3931 s 3H Jlml CH2 Im HzN c coon IIIN O COOH H H mm mm Nonypoiar and unreactive very reattwe The suifur can not be protonated Acts as a nucieopniie a iittie he CH2 can ionize at miid aikaiine conditions Disulfide bonds can form between two cysteine residues in deprotonating conditions The cysteines will lose their H s when in a pH above 7 To break the bond decrease pH below 7 1 2 uo N I e I I Eneg m u T In Q m m u tn1 7 l quot5 disuiiide z 77 0 bond cysteine d fr 1 fr F r g Hfij T Kayx V 11 1 F 59 mm L f J Abwnd mw i39f waginga Wax mmvcs W mgh 925ng ms 1639 39 v19 3 mm mm iiwwwmmmm quot Wagth rgsrah ywim ammgim ug i 1 W 39 r9 who MWQJMQ gigwma Mo rawml y an f s J a arm rlg mam 1 irwmwmpmwi gww kgms AM 3 ml l fsm mam 34 w 1 2 0 Wag g as high mamm my x 145 mu gummim g ihimgik army wngtgwad mvaga m smssmg r pryE H 31 may m M v fuammmi sag Rm A3 wmuamg ism a gmiwg aim marmwy WUI39 quot QWQQWQ quot Th3 Wquot 39 39 39 arr rigmdl tgd Imam3 ale mgw WQWEWQMR mm 93 Discriminationrecognition With all this In mind it is clear that many delicate contributions shape the precision of recognition between each response regulator and its cognate kinase The um similarities wart f struct that the overall tertiary ohm the protein is not the dominant component for recognition Invest ate the character and variant of the surfeoe presented by the response regulator Subclassifcation of response regulators using the surface characteristics of their W Response regulators usually have Mo domains N terminal receiver domain gets phosphorylated Cterminal output domain gets released and goes all to do it39s transcriptional role by binding to a pmmoter Response regulators have been classi ed by their output domains Can you classify them by their receiver domains and then subclassify What criteria can we use to potentially do this w w x A 6X Ks giimmimwrw r gym22w w j m L37 r 7m mmigm RR mlg1r g 7 T quot3 r r if r v x Vquot l E 3 m g mm v J A1110 A hydrophobicity less ILV GAF CM ST W IPH L53 n qQR prmw mgummwg Hiy d gl SWEW 5meng s V WEQCC J WMquot 9r W39th more hydrophobicity less ILV GAF CM ST WYPH mtg E m R R m 1331UJH3913 W 1 Hydhr 1 39t i E35 more hydrophobicity less ILV GAF CM ST WYPH b J Overall the cithelix 11helix 0i5heix Interactions from the cithelix of interface contribute 75 of the interactions CheY to CheZ constitute 70 of the between SpoOF and the helix in SpoOB defined contacts LHJgVy1fgr l m 3 WWW W i a 39 mm w m quotmusic3 39 soJain mme rm Mm mmm mm m mmwmm MW am 3 a L m Ramp anhrgdxr magma WM m mm mmmm 1m mag cm i i miow 1397 i E jaguawr chi us nuns 1 gtStzip lay115 a S p 2 15451 A I 7 Strup 3 JAN2 2 1 2 3 M an hy xuphuhi tats content R25 is subtllxs strip analysi s 1 r m a bum V x I strip analysis x V I B gtStrip DH2 1 Strip 2 544513 7 2 3 Strip 3 224113 7 came mm A x 2 X quot me hydrophoblcitv K x 2 J J ILV GAP CM ST WYPH 339 m 0011043 7 445m T J 9quot Smp 205m avg Am mm comer I 2 2 PM 2 52551115 522005 000 7 5 ho I0 47 L7 2 I 0 2 2 mm mm 250 I0 47 20 2 I I 0 2 r 52222 1 urn2 2 I ycF I5 47 25 2 2 0 I 2 K s p 2 5545 47 ss I0 47 00 2 I 0 0 2 m2qu 2 27 pa I0 50 00 2 I 0 0 I kept I0 42 20 4 I 0 0 2 5275 2mm 222222252 mp I0 47 00 2 I 0 0 I 552522 0222 um I0 47 20 2 I I 0 2 k 2 cm 20 22 20 I I I I 2 00 I0 25 25 I I 2 2 2 er I0 42 40 2 2 I 0 2 I54 25 50 20 2 2 0 I I m 20 47 00 2 2 0 0 I m I0 20 00 2 I 0 I 2 chI I0 20 00 I I 0 n 2 5527202 2 00 yea I0 25 I0 I I I I 2 ed I0 22 I0 I 2 0 2 2 0554 I0 20 00 I I 0 I 2 00R I0 20 00 I I 0 I 2 m4 I0 22 40 2 I 0 2 2 0m I0 20 25 2 0 0 2 2 dpE I0 45 20 2 2 0 I I ma I0 42 25 2 2 I 0 2 ask In 4 40 5 I 0 I I pXR In 50 20 2 0 I 0 I hoF In 47 50 4 I 0 0 I sea In 47 25 4 I 0 I I 504 I5 50 40 2 I 0 I I ae I0 47 00 2 I 0 0 2 mpFl A I0 50 00 2 I 0 0 2 Bacillus subtilis Escherichia coli G more hydrophobicity less lLV GAF CM ST WYPH 5 4 3 II M mn Inn Insu IIPK IIIK L1 IIIm1 on 3 than 3 II I IAI nun Hm I I rum IAI hl Illllla 4 I39m 1 I M I H Illa J mm 139 mu t39 Tubal l a MJ 1 I Al I39 v n um u I I I II Hull In I I I mu IIHL I I I Al I I bll IIquot M 39 I I o no IIH II nun IN l mu Illllsu I m lIII mm IM 0 IIrI I I u d IIHL la 4 IM l39 udl quotH II quotplIII mom I I I ll la I M I Int 1 I M a mu III I l l I M39 Ill k I I I M D I D IIIIL u I l I ma Ilai I M I M mu 4 I M D M III39K I4 I M l39 lull I h I M II M IIH a I A h Inn uh I I M 139 lax III39I II Inal quotMll un39 D J Komm R J fhompson J Cavanagh FEES Lsft 554 231 2003 Conclusions a wmwmmcg mmta mlmggj mme x caib 19 EM WLNP J R RR mm a ngg mg y 1mm amjuz o x gjjm ngmggmgg ag maw mw wm am ltYi9r gt M151 mig mm mg mmium jmu f a mrghsrg Qmmmmm wmm mmmmu fag 3 NW 39 mg f gy bqg gcg i y bmgg Myh ry lrgllirfha mmm a kwg g myiiilsgika r mmurw wa amattys gi 3 139 glam 1mm 34 mg gim g Mic 6 mg 9016731331