EzCatDB: D00271

DB codeD00271
RLCP classification6.30.93020.5311
8.12111.792000.5722
8.11211.912000.5525
6.40.508000.5522
CATH domainDomain 13.20.20.10Catalytic domain
Domain 22.40.37.10Catalytic domain
E.C.5.1.1.1
CSA1bd0
MACiEM0213

CATH domainRelated DB codes (homologues)
2.40.37.10D00251
3.20.20.10D00251

Enzyme Name
Swiss-protKEGG

P10724Q9HTQ2Q65YW7P0A4X2
Protein nameAlanine racemaseAlanine racemase, catabolicAlanine racemaseAlanine racemasealanine racemase
L-alanine racemase
SynonymsEC 5.1.1.1
EC 5.1.1.1
EC 5.1.1.1
EC 5.1.1.1

KEGG pathways
MAP codePathways
MAP00252Alanine and aspartate metabolism
MAP00473D-Alanine metabolism

Swiss-prot:Accession NumberP10724Q9HTQ2Q65YW7P0A4X2
Entry nameALR_BACSTALR2_PSEAEQ65YW7_STRLAALR_MYCTU
ActivityL-alanine = D-alanine.L-alanine = D-alanine.L-alanine = D-alanine.L-alanine = D-alanine.
SubunitHomodimer.


Subcellular location



CofactorPyridoxal phosphate.Pyridoxal phosphate (By similarity).Pyridoxal phosphate.,Pyridoxal phosphate (By similarity).Pyridoxal phosphate (By similarity).


CofactorsSubstratesProductsintermediates
KEGG-idC00018C00041C00133


CompoundPyridoxal phosphateL-AlanineD-AlanineExternal aldimine intermediate-1 Quinonoid intermediateExternal aldimine intermediate-2
Typearomatic ring (with nitrogen atoms),phosphate group/phosphate ionamino acidsamino acids


1bd0A01Analogue:IN5UnboundUnboundIntermediate-analogue:IN5UnboundUnbound
1bd0B01Analogue:IN5UnboundUnboundIntermediate-analogue:IN5UnboundUnbound
1epvA01Analogue:DCSUnboundUnboundUnboundIntermediate-analogue:DCSUnbound
1epvB01Analogue:DCSUnboundUnboundUnboundIntermediate-analogue:DCSUnbound
1ftxA01Analogue:EPCUnboundUnboundUnboundUnboundIntermediate-analogue:EPC
1ftxB01Analogue:EPCUnboundUnboundUnboundUnboundIntermediate-analogue:EPC
1l6fA01Analogue:PP3UnboundUnboundIntermediate-bound:PP3UnboundUnbound
1l6fB01Analogue:PP3UnboundUnboundIntermediate-bound:PP3UnboundUnbound
1l6gA01Analogue:PDDUnboundUnboundUnboundUnboundIntermediate-bound:PDD
1l6gB01Analogue:PDDUnboundUnboundUnboundUnboundIntermediate-bound:PDD
1niuA01Analogue:DCSUnboundUnboundUnboundIntermediate-analogue:DCSUnbound
1niuB01Analogue:DCSUnboundUnboundUnboundIntermediate-analogue:DCSUnbound
1sftA01Bound:PLPUnboundUnboundUnboundUnboundUnbound
1sftB01Bound:PLPUnboundUnboundUnboundUnboundUnbound
1xqkA01Analogue:PMHUnboundUnboundUnboundIntermediate-analogue:PMHUnbound
1xqkB01Analogue:PMHUnboundUnboundUnboundIntermediate-analogue:PMHUnbound
1xqlA01Analogue:PLP-PMH-PMPUnboundUnboundUnboundIntermediate-analogue:PMHIntermediate-analogue:PMP-4AX
1xqlB01Analogue:PLP-PMH-PMPUnboundUnboundUnboundIntermediate-analogue:PMHIntermediate-analogue:PMP-4AX
2sfpA01Bound:PLPUnboundUnboundUnboundUnboundUnbound
2sfpB01Bound:PLPUnboundUnboundUnboundUnboundUnbound
1rcqA01Bound:PLPUnboundUnboundUnboundUnboundUnbound
1vfhA01Bound:PLPUnboundUnboundUnboundUnboundUnbound
1vfsA01Analogue:DCSUnboundUnboundUnboundIntermediate-analogue:DCSUnbound
1vfsB01Analogue:DCSUnboundUnboundUnboundIntermediate-analogue:DCSUnbound
1vftA01Analogue:DCSUnboundUnboundUnboundIntermediate-analogue:DCSUnbound
1vftB01Analogue:DCSUnboundUnboundUnboundIntermediate-analogue:DCSUnbound
1xfcA01Bound:PLPUnboundUnboundUnboundUnboundUnbound
1xfcB01Bound:PLPUnboundUnboundUnboundUnboundUnbound
1bd0A02UnboundUnboundUnboundUnboundUnboundUnbound
1bd0B02UnboundUnboundUnboundUnboundUnboundUnbound
1epvA02UnboundUnboundUnboundUnboundUnboundUnbound
1epvB02UnboundUnboundUnboundUnboundUnboundUnbound
1ftxA02UnboundUnboundUnboundUnboundUnboundUnbound
1ftxB02UnboundUnboundUnboundUnboundUnboundUnbound
1l6fA02UnboundUnboundUnboundUnboundUnboundUnbound
1l6fB02UnboundUnboundUnboundUnboundUnboundUnbound
1l6gA02UnboundUnboundUnboundUnboundUnboundUnbound
1l6gB02UnboundUnboundUnboundUnboundUnboundUnbound
1niuA02UnboundUnboundUnboundUnboundUnboundUnbound
1niuB02UnboundUnboundUnboundUnboundUnboundUnbound
1sftA02UnboundAnalogue:ACTUnboundUnboundUnboundUnbound
1sftB02UnboundAnalogue:ACTUnboundUnboundUnboundUnbound
1xqkA02UnboundUnboundUnboundUnboundUnboundUnbound
1xqkB02UnboundUnboundUnboundUnboundUnboundUnbound
1xqlA02UnboundAnalogue:ACYUnboundUnboundUnboundUnbound
1xqlB02UnboundAnalogue:ACYUnboundUnboundUnboundUnbound
2sfpA02UnboundAnalogue:PPIUnboundUnboundUnboundUnbound
2sfpB02UnboundAnalogue:PPIUnboundUnboundUnboundUnbound
1rcqA02UnboundUnboundAnalogue:DLYUnboundUnboundUnbound
1vfhA02UnboundUnboundUnboundUnboundUnboundUnbound
1vfsA02UnboundUnboundUnboundUnboundUnboundUnbound
1vfsB02UnboundUnboundUnboundUnboundUnboundUnbound
1vftA02UnboundUnboundUnboundUnboundUnboundUnbound
1vftB02UnboundUnboundUnboundUnboundUnboundUnbound
1xfcA02UnboundUnboundUnboundUnboundUnboundUnbound
1xfcB02UnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P10724 & literature [18]
pdbCatalytic residuesCofactor-binding residuesModified residuescomment
1bd0A01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)


1bd0B01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)


1epvA01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

1epvB01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

1ftxA01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

1ftxB01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

1l6fA01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

1l6fB01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

1l6gA01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

1l6gB01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

1niuA01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

1niuB01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

1sftA01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)


1sftB01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)


1xqkA01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

1xqkB01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

1xqlA01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

1xqlB01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

2sfpA01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

2sfpB01LYS   39;HIS  166;ARG  219
LYS   39(PLP binding)
KCX  129(carbamylated Lys)

1rcqA01LYS   33;HIS  158;ARG  208
LYS   33(PLP binding)
KCX  122(carbamylated Lys)

1vfhA01LYS   38;HIS  168;ARG  224
LYS   38(PLP binding)
KCX  129(carbamylated Lys)

1vfsA01LYS   38;HIS  168;ARG  224
LYS   38(PLP binding)
KCX  129(carbamylated Lys)

1vfsB01LYS 1038;HIS 1168;ARG 1224
LYS 1038(PLP binding)
KCX 1129(carbamylated Lys)

1vftA01LYS   38;HIS  168;ARG  224
LYS   38(PLP binding)
KCX  129(carbamylated Lys)

1vftB01LYS 1038;HIS 1168;ARG 1224
LYS 1038(PLP binding)
KCX 1129(carbamylated Lys)

1xfcA01LYS   42;HIS  172;ARG  228
LYS   42(PLP binding)


1xfcB01LYS   42;HIS  172;ARG  228
LYS   42(PLP binding)


1bd0A02TYR  265;ASP  313



1bd0B02TYR  265;ASP  313



1epvA02TYR  265;ASP  313



1epvB02TYR  265;ASP  313



1ftxA02TYR  265;ASP  313



1ftxB02TYR  265;ASP  313



1l6fA02TYR  265;ASP  313



1l6fB02TYR  265;ASP  313



1l6gA02TYR  265;ASP  313



1l6gB02TYR  265;ASP  313



1niuA02TYR  265;ASP  313



1niuB02TYR  265;ASP  313



1sftA02TYR  265;ASP  313



1sftB02TYR  265;ASP  313



1xqkA02        ;ASP  313


mutant Y265F
1xqkB02        ;ASP  313


mutant Y265F
1xqlA02        ;ASP  313


mutant Y265F
1xqlB02        ;ASP  313


mutant Y265F
2sfpA02TYR  265;ASP  313



2sfpB02TYR  265;ASP  313



1rcqA02TYR  253;ASP  302



1vfhA02TYR  270;ASP  319



1vfsA02TYR  270;ASP  319



1vfsB02TYR 1270;ASP 1319



1vftA02TYR  270;ASP  319



1vftB02TYR 1270;ASP 1319



1xfcA02TYR  271;ASP  320



1xfcB02        ;ASP  320


invisible 264-278

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[8]Fig.7, p.1334-1341
[9]Scheme 1, p.10441-10443
[10]p.3295-3300
[11]Scheme 1, Scheme 2, p.4064-4065
[12]Fig.1
[13]Fig.1
[14]Scheme I, Scheme II, p.4193-4194
[17]p.2832-3834
[18]Scheme I, Scheme II, p.19169-10172
[21]Fig.5, p.5104-5107
[27]Fig 9, Fig.11, p.284-286

references
[1]
PubMed ID7034778
JournalBiochemistry
Year1981
Volume20
Pages7539-46
AuthorsWang EA, Walsh C
TitleCharacteristics of beta, beta-difluoroalanine and beta, beta, beta -trifluoroalanine as suicide substrates for Escherichia coli B alanine racemase.
[2]
PubMed ID6427785
JournalProg Clin Biol Res
Year1984
Volume144A
Pages339-50
AuthorsJohnston RB, Schreiber EC, Davis MP, Jillson L, Sorrell WT, Kirker ME
TitleCatalytic properties of the active site of alanine racemase from B. subtilis.
[3]
PubMed ID3730360
JournalBiochemistry
Year1986
Volume25
Pages3275-82
AuthorsBadet B, Inagaki K, Soda K, Walsh CT
TitleTime-dependent inhibition of Bacillus stearothermophilus alanine racemase by (1-aminoethyl)phosphonate isomers by isomerization to noncovalent slowly dissociating enzyme-(1-aminoethyl)phosphonate complexes.
[4]
PubMed ID3118951
JournalBiochemistry
Year1987
Volume26
Pages5878-84
AuthorsMobashery S, Johnston M
TitleInactivation of alanine racemase by beta-chloro-L-alanine released enzymatically from amino acid and peptide C10-esters of deacetylcephalothin.
[5]
PubMed ID3680197
JournalJ Biol Chem
Year1987
Volume262
Pages15323-6
AuthorsNeidhart DJ, Distefano MD, Tanizawa K, Soda K, Walsh CT, Petsko GA
TitleX-ray crystallographic studies of the alanine-specific racemase from Bacillus stearothermophilus. Overproduction, crystallization, and preliminary characterization.
[6]
PubMed ID3167024
JournalBiochemistry
Year1988
Volume27
Pages4966-70
AuthorsCopie V, Faraci WS, Walsh CT, Griffin RG
TitleInhibition of alanine racemase by alanine phosphonate: detection of an imine linkage to pyridoxal 5'-phosphate in the enzyme-inhibitor complex by solid-state 15N nuclear magnetic resonance.
[7]
PubMed ID2690935
JournalBiochemistry
Year1989
Volume28
Pages8167-74
AuthorsGalakatos NG, Walsh CT
TitleMutations at the interdomain hinge region of the DadB alanine racemase: effects of length and conformational constraint of the linker sequence on catalytic efficiency.
[8]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), AND REVISIONS.
Medline ID97178818
PubMed ID9063881
JournalBiochemistry
Year1997
Volume36
Pages1329-42
AuthorsShaw JP, Petsko GA, Ringe D
TitleDetermination of the structure of alanine racemase from Bacillus stearothermophilus at 1.9-A resolution.
Related PDB1sft
Related Swiss-protP10724
[9]
CommentsX-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
Medline ID98337786
PubMed ID9671513
JournalBiochemistry
Year1998
Volume37
Pages10438-45
AuthorsStamper GF, Morollo AA, Ringe D, Stamper CG
TitleReaction of alanine racemase with 1-aminoethylphosphonic acid forms a stable external aldimine.
Related PDB1bd0
Related Swiss-protP10724
[10]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID99178834
PubMed ID10079072
JournalBiochemistry
Year1999
Volume38
Pages3293-301
AuthorsMorollo AA, Petsko GA, Ringe D
TitleStructure of a Michaelis complex analogue: propionate binds in the substrate carboxylate site of alanine racemase.
Related PDB2sfp
Related Swiss-protP10724
[11]
CommentsMUTAGENESIS OF ARG-219.
Medline ID99212226
PubMed ID10194319
JournalBiochemistry
Year1999
Volume38
Pages4058-65
AuthorsSun S, Toney MD
TitleEvidence for a two-base mechanism involving tyrosine-265 from arginine-219 mutants of alanine racemase.
Related Swiss-protP10724
[12]
PubMed ID10348897
JournalJ Biochem (Tokyo)
Year1999
Volume125
Pages987-90
AuthorsWatanabe A, Kurokawa Y, Yoshimura T, Esaki N
TitleRole of tyrosine 265 of alanine racemase from Bacillus stearothermophilus.
[13]
CommentsACTIVE SITES, AND MUTAGENESIS.
Medline ID99434146
PubMed ID10502689
JournalJ Biochem (Tokyo)
Year1999
Volume126
Pages781-6
AuthorsWatanabe A, Yoshimura T, Mikami B, Esaki N
TitleTyrosine 265 of alanine racemase serves as a base abstracting alpha-hydrogen from L-alanine: the counterpart residue to lysine 39 specific to D-alanine.
Related Swiss-protP10724
[14]
PubMed ID9933615
JournalJ Biol Chem
Year1999
Volume274
Pages4189-94
AuthorsWatanabe A, Kurokawa Y, Yoshimura T, Kurihara T, Soda K, Esaki N, Watababe A
TitleRole of lysine 39 of alanine racemase from Bacillus stearothermophilus that binds pyridoxal 5'-phosphate. Chemical rescue studies of Lys39 --> Ala mutant.
[15]
PubMed ID11064190
JournalFEMS Microbiol Lett
Year2000
Volume192
Pages169-73
AuthorsOkubo Y, Yokoigawa K, Esaki N, Soda K, Misono H
TitleHigh catalytic activity of alanine racemase from psychrophilic Bacillus psychrosaccharolyticus at high temperatures in the presence of pyridoxal 5'-phosphate.
[16]
PubMed ID10673430
JournalStructure Fold Des
Year2000
Volume8
PagesR1-6
AuthorsSchneider G, Kack H, Lindqvist Y
TitleThe manifold of vitamin B6 dependent enzymes.
[17]
PubMed ID11456969
JournalJ Am Chem Soc
Year2001
Volume123
Pages2830-4
AuthorsOndrechen MJ, Briggs JM, McCammon JA
TitleA model for enzyme-substrate interaction in alanine racemase.
[18]
CommentsX-ray crystallography
PubMed ID11886871
JournalJ Biol Chem
Year2002
Volume277
Pages19166-72
AuthorsWatanabe A, Yoshimura T, Mikami B, Hayashi H, Kagamiyama H, Esaki N
TitleReaction mechanism of alanine racemase from Bacillus stearothermophilus: x-ray crystallographic studies of the enzyme bound with N-(5'-phosphopyridoxyl)alanine.
Related PDB1l6f,1l6g
[19]
CommentsX-ray crystallography
PubMed ID12741835
JournalBiochemistry
Year2003
Volume42
Pages5775-83
AuthorsFenn TD, Stamper GF, Morollo AA, Ringe D
TitleA side reaction of alanine racemase: transamination of cycloserine.
Related PDB1epv,1niu
[20]
PubMed ID14674749
JournalBiochemistry
Year2003
Volume42
Pages14752-61
AuthorsLeMagueres P, Im H, Dvorak A, Strych U, Benedik M, Krause KL
TitleCrystal structure at 1.45 A resolution of alanine racemase from a pathogenic bacterium, Pseudomonas aeruginosa, contains both internal and external aldimine forms.
Related PDB1rcq
[21]
PubMed ID12718553
JournalBiochemistry
Year2003
Volume42
Pages5099-107
AuthorsSpies MA, Toney MD
TitleMultiple hydrogen kinetic isotope effects for enzymes catalyzing exchange with solvent: application to alanine racemase.
[22]
PubMed ID12686135
JournalBiochim Biophys Acta
Year2003
Volume1647
Pages214-9
AuthorsPaiardini A, Contestabile R, D'Aguanno S, Pascarella S, Bossa F
TitleThreonine aldolase and alanine racemase: novel examples of convergent evolution in the superfamily of vitamin B6-dependent enzymes.
[23]
PubMed ID14517907
JournalBiopolymers
Year2003
Volume70
Pages186-200
AuthorsMustata GI, Soares TA, Briggs JM
TitleMolecular dynamics studies of alanine racemase: a structural model for drug design.
[24]
PubMed ID12725937
JournalFEMS Microbiol Lett
Year2003
Volume221
Pages263-7
AuthorsYokoigawa K, Okubo Y, Soda K
TitleSubunit interaction of monomeric alanine racemases from four Shigella species in catalytic reaction.
[25]
PubMed ID15302886
JournalJ Biol Chem
Year2004
Volume279
Pages46153-61
AuthorsNoda M, Matoba Y, Kumagai T, Sugiyama M
TitleStructural evidence that alanine racemase from a D-cycloserine-producing microorganism exhibits resistance to its own product.
Related PDB1vfh,1vfs,1vft
[26]
PubMed ID15115851
JournalProtein Eng Des Sel
Year2004
Volume17
Pages223-34
AuthorsMustata G, Briggs JM
TitleCluster analysis of water molecules in alanine racemase and their putative structural role.
[27]
PubMed ID15581583
JournalArch Biochem Biophys
Year2005
Volume433
Pages279-87
AuthorsToney MD
TitleReaction specificity in pyridoxal phosphate enzymes.
[28]
CommentsX-ray crystallography
PubMed ID15807525
JournalBiochemistry
Year2005
Volume44
Pages5317-27
AuthorsFenn TD, Holyoak T, Stamper GF, Ringe D
TitleEffect of a Y265F Mutant on the Transamination-Based Cycloserine Inactivation of Alanine Racemase.
Related PDB1xqk,1xql
[29]
PubMed ID15683232
JournalBiochemistry
Year2005
Volume44
Pages1471-81
AuthorsLeMagueres P, Im H, Ebalunode J, Strych U, Benedik MJ, Briggs JM, Kohn H, Krause KL
TitleThe 1.9 A crystal structure of alanine racemase from Mycobacterium tuberculosis contains a conserved entryway into the active site.
Related PDB1xfc

comments
This enzyme belongs to the type-III PLP-dependent enzyme superfamily.
This enzyme catalyzes racemization, which is composed of the following reactions (see [8], [11], [14], [18], [21] & [27]):
(A) Formation of external aldimine (with amine group of L-Ala),
(B) Isomerization (change in the position of double-bond), forming a quinonoid intermediate.
(C) Isomerization (change in the position of double-bond).
(D) Formation of internal aldimine, leading to the release of the product from PLP.
These reactions proceed in the following way:
(A) Formation of external aldimine (with amine group of L-Ala) (see [8], [11], [14], [18], [21] & [27]);
(A1) The interaction of Arg219 through His166 with Tyr265' (from the adjacent chain) keeps the sidechain of Tyr265' unprotonated. (Arg219/His166 act as modulators.) In addition, Asp313' may modulate the activity of Lys39.
(A2) Tyr265' acts as a general base to deprotonate and activate the protonated amine group of substrate, L-Ala.
(A3) The deprotonated amine group of L-Ala makes a nucleophilic attack on the C4' atom of PLP, which forms an internal aldimine with Lys39, forming a transient geminal diamine intermediate.
(A4) Proton transfer from the amine group of L-Ala to epsilon-nitrogen atom of Lys39 must occur (probably through alpha-carboxyl group, or C4' atom of PLP).
(A5) The lone pair of the amine group of L-Ala makes the second nucleophilic attack on the C4' atom, leading to the formation of the external aldimine with L-Ala and the release of Lys39 (unprotonated).
(B) Isomerization (change in the position of double-bond), forming a quinonoid intermediate (see [8], [11], [14], [18], [21] & [27]);
(B1) Protonated Tyr265' must be deprotonated, whereas unprotonated Lys39 must be protonated. Here, alpha-carboxyl group of L-Ala=PLP might acts as a base-acid, which deprotonates the sidechain of Tyr265' and protonates that of Lys39 (see [18]). Here, Arg219/His166 may modulate the activity of Tyr265'.
(B2) Tyr265' acts as a general base to deprotonate the alpha-proton of the L-amino acid substrate, forming a quinonoid intermediate (or carbanion intermediate).
(B3) Arg219 interacts with the N1 atom of PLP, modulating and decreasing (or destabilizing) the activity of the PLP cofactor as an electron sink, which destabilizes quinonoid intermediate and facilitates the next step of reprotonation of alpha-carbon (see [8]).
(C) Isomerization (change in the position of double-bond): (Inverse reaction of (B))
(C1) Arg219 interacts with the N1 atom of PLP, modulating and decreasing (or destabilizing) the activity of the PLP cofactor as an electron sink, which destabilizes quinonoid intermediate and facilitates the this step. In addition, Asp313' may modulate the activity of Lys39.
(C2) Lys39 acts as a general acid to protonate the alpha-carbon of the L-amino acid substrate from the opposite side of Tyr265' (from re face of PLP). This reaction leads to the formation of the external aldimine of D-Ala with PLP.
(D) Formation of internal aldimine, leading to the elimination of the product from PLP: (Inverse reaction of (A));
(D1) Asp313' may modulate the activity of Lys39.
(D2) The deprotonated amine group of Lys39 makes a nucleophilic attack on the C4' carbon of the PLP of the external aldimine, forming a transient geminal diamine intermediate.
(D2) Proton transfer from the epsilon-nitrogen atom of Lys39 to the amine group of D-Ala must occur (probably through alpha-carboxyl group, or C4' atom of PLP).
(D3) The lone pair of the amine nitrogen of Lys39 can attack on the C4' atom to form a double-bond, and to release the amine of the product, D-Ala.
(D4) The interaction of Arg219 through His166 with Tyr265' (from the adjacent chain) assists Tyr265' in acting as a general acid to protonate the amine group of the product. (Arg219/His166 act as modulators.)

createdupdated
2005-04-182009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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