EzCatDB: D00248

DB codeD00248
RLCP classification1.20.30800.980
CATH domainDomain 13.40.50.1000Catalytic domain
Domain 21.10.164.10Catalytic domain
E.C.3.8.1.2
CSA1qh9,1qq5
MACiEM0036

CATH domainRelated DB codes (homologues)
3.40.50.1000M00102

Enzyme Name
Swiss-protKEGG

Q53464Q60099
Protein name(S)-2-haloacid dehalogenase(S)-2-haloacid dehalogenase(S)-2-haloacid dehalogenase
2-haloacid dehalogenase[ambiguous]
2-haloacid halidohydrolase [ambiguous][ambiguous]
2-haloalkanoic acid dehalogenase
2-haloalkanoid acid halidohydrolase
2-halocarboxylic acid dehalogenase II
DL-2-haloacid dehalogenase[ambiguous]
L-2-haloacid dehalogenase
L-DEX
SynonymsEC 3.8.1.2
2-haloalkanoic acid dehalogenase
L-2-haloacid dehalogenase
Halocarboxylic acid halidohydrolase
L-DEX
EC 3.8.1.2
2-haloalkanoic acid dehalogenase
L-2-haloacid dehalogenase
Halocarboxylic acid halidohydrolase

KEGG pathways
MAP codePathways
MAP00361gamma-Hexachlorocyclohexane degradation
MAP006311,2-Dichloroethane degradation

Swiss-prot:Accession NumberQ53464Q60099
Entry nameHAD_PSEUYHAD_XANAU
Activity(S)-2-haloacid + H(2)O = (R)-2-hydroxyacid + halide.(S)-2-haloacid + H(2)O = (R)-2-hydroxyacid + halide.
SubunitHomodimer.Homodimer.
Subcellular location

Cofactor



SubstratesProductsintermediates
KEGG-idC02103C00001C02489C00462
Compound(S)-2-HaloacidH2O(R)-2-HydroxyacidHalide
Typecarboxyl group,halideH2Ocarbohydrate,carboxyl grouphalide
1aq6A01Analogue:FMT 2
UnboundUnboundUnbound
1aq6B01Analogue:FMT 1
UnboundUnboundUnbound
1judA01Unbound
UnboundUnboundUnbound
1qh9A01Unbound
Bound:LACUnboundUnbound
1qq5A01Analogue:FMT
UnboundUnboundUnbound
1qq5B01Analogue:FMT
UnboundUnboundUnbound
1qq6A01UnboundUnboundUnboundUnboundIntermediate-bound:ASB
1qq6B01UnboundUnboundUnboundUnboundIntermediate-bound:ASB
1qq7A01Unbound
UnboundUnboundIntermediate-bound:ASB
1qq7B01Unbound
UnboundUnboundIntermediate-bound:ASB
1zrmA01UnboundBound:HOH 500UnboundUnboundIntermediate-bound:BUA
1zrnA01UnboundBound:HOH 500UnboundUnboundIntermediate-bound:ACY
1aq6A02Analogue:FMT
UnboundUnboundUnbound
1aq6B02Unbound
UnboundUnboundUnbound
1judA02Unbound
UnboundUnboundUnbound
1qh9A02Unbound
UnboundUnboundUnbound
1qq5A02Unbound
UnboundUnboundUnbound
1qq5B02Unbound
UnboundUnboundUnbound
1qq6A02Unbound
UnboundBound:_CLUnbound
1qq6B02Unbound
UnboundBound:_CLUnbound
1qq7A02Unbound
UnboundBound:_CLUnbound
1qq7B02Unbound
UnboundBound:_CLUnbound
1zrmA02Unbound
UnboundUnboundUnbound
1zrnA02Unbound
UnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;Q53464, Q60099 & literature [10], [13] & [16]
pdbCatalytic residuesModified residuescomment
1aq6A01ASP  8;THR 12;LYS 147;TYR 153;SER 171;ASN 173;ASP 176


1aq6B01ASP  8;THR 12;LYS 147;TYR 153;SER 171;ASN 173;ASP 176


1judA01ASP 10;THR 14;LYS 151;TYR 157;SER 175;ASN 177;ASP 180


1qh9A01ASP 10;THR 14;LYS 151;TYR 157;SER 175;ASN 177;ASP 180


1qq5A01ASP  8;THR 12;LYS 147;TYR 153;SER 171;ASN 173;ASP 176


1qq5B01ASP  8;THR 12;LYS 147;TYR 153;SER 171;ASN 173;ASP 176


1qq6A01      ;THR 12;LYS 147;TYR 153;SER 171;ASN 173;ASP 176
ASB 8(aspartic acid-4-carboxymethyl ester)

1qq6B01      ;THR 12;LYS 147;TYR 153;SER 171;ASN 173;ASP 176
ASB 8(aspartic acid-4-carboxymethyl ester)

1qq7A01      ;THR 12;LYS 147;TYR 153;SER 171;ASN 173;ASP 176
ASB 8(aspartic acid-4-carboxymethyl ester)

1qq7B01      ;THR 12;LYS 147;TYR 153;SER 171;ASN 173;ASP 176
ASB 8(aspartic acid-4-carboxymethyl ester)

1zrmA01ASP 10;THR 14;LYS 151;TYR 157;       ;ASN 177;ASP 180

mutant S175A
1zrnA01ASP 10;THR 14;LYS 151;TYR 157;       ;ASN 177;ASP 180

mutant S175A
1aq6A02ARG 39


1aq6B02ARG 39


1judA02ARG 41


1qh9A02ARG 41


1qq5A02ARG 39


1qq5B02ARG 39


1qq6A02ARG 39


1qq6B02ARG 39


1qq7A02ARG 39


1qq7B02ARG 39


1zrmA02ARG 41


1zrnA02ARG 41



References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Fig.6, p.494
[2]Fig.1
[3]Fig.2, p.1321
[6]p.20328-20329
[8]p.33020-33021
[9]p.21
[10]Fig.8, p.15041-15043
[13]Fig.5, p.30676-30677
[16]SCHEME 1

references
[1]
PubMed ID8216900
JournalBiol Chem Hoppe Seyler
Year1993
Volume374
Pages489-96
AuthorsSchneider B, Muller R, Frank R, Lingens F
TitleSite-directed mutagenesis of the 2-haloalkanoic acid dehalogenase I gene from Pseudomonas sp. strain CBS3 and its effect on catalytic activity.
[2]
PubMed ID7822238
JournalJ Biochem (Tokyo)
Year1994
Volume116
Pages248-9
AuthorsLiu JQ, Kurihara T, Esaki N, Soda K
TitleReconsideration of the essential role of a histidine residue of L-2-halo acid dehalogenase.
[3]
CommentsMUTAGENESIS.
Medline ID96105006
PubMed ID7490277
JournalJ Biochem (Tokyo)
Year1995
Volume117
Pages1317-22
AuthorsKurihara T, Liu JQ, Nardi-Dei V, Koshikawa H, Esaki N, Soda K
TitleComprehensive site-directed mutagenesis of L-2-halo acid dehalogenase to probe catalytic amino acid residues.
Related Swiss-protQ53464
[4]
PubMed ID8580854
JournalProtein Sci
Year1995
Volume4
Pages2619-20
AuthorsRidder IS, Rozeboom HJ, Kingma J, Janssen DB, Dijkstra BW
TitleCrystallization and preliminary X-ray analysis of L-2-haloacid dehalogenase from Xanthobacter autotrophicus GJ10.
[5]
PubMed ID8607850
JournalBiochem Biophys Res Commun
Year1996
Volume220
Pages828-33
AuthorsDiez A, Prieto MI, Alvarez MJ, Bautista JM, Garrido J, Puyet A
TitleImproved catalytic performance of a 2-haloacid dehalogenase from Azotobacter sp. by ion-exchange immobilisation.
[6]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID96355356
PubMed ID8702766
JournalJ Biol Chem
Year1996
Volume271
Pages20322-30
AuthorsHisano T, Hata Y, Fujii T, Liu JQ, Kurihara T, Esaki N, Soda K
TitleCrystal structure of L-2-haloacid dehalogenase from Pseudomonas sp. YL. An alpha/beta hydrolase structure that is different from the alpha/beta hydrolase fold.
Related PDB1jud
Related Swiss-protQ53464
[7]
PubMed ID8860001
JournalProteins
Year1996
Volume24
Pages520-2
AuthorsHisano T, Hata Y, Fujii T, Liu JQ, Kurihara T, Esaki N, Soda K
TitleCrystallization and preliminary x-ray crystallographic studies of L-2-haloacid dehalogenase from Pseudomonas sp. YL.
[8]
CommentsX-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) AND REVISION TO 84
Medline ID98070500
PubMed ID9407083
JournalJ Biol Chem
Year1997
Volume272
Pages33015-22
AuthorsRidder IS, Rozeboom HJ, Kalk KH, Janssen DB, Dijkstra BW
TitleThree-dimensional structure of L-2-haloacid dehalogenase from Xanthobacter autotrophicus GJ10 complexed with the substrate-analogue formate.
Related PDB1aq6
Related Swiss-protQ60099
[9]
PubMed ID9644239
JournalJ Biochem (Tokyo)
Year1998
Volume124
Pages20-2
AuthorsLi YF, Hata Y, Fujii T, Kurihara T, Esaki N
TitleX-ray structure of a reaction intermediate of L-2-haloacid dehalogenase with L-2-chloropropionamide.
[10]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID98279020
PubMed ID9614112
JournalJ Biol Chem
Year1998
Volume273
Pages15035-44
AuthorsLi YF, Hata Y, Fujii T, Hisano T, Nishihara M, Kurihara T, Esaki N
TitleCrystal structures of reaction intermediates of L-2-haloacid dehalogenase and implications for the reaction mechanism.
Related PDB1zrm,1zrn
Related Swiss-protQ53464
[11]
PubMed ID10191250
JournalBiochem J
Year1999
Volume339
Pages223-6
AuthorsRidder IS, Dijkstra BW
TitleIdentification of the Mg2+-binding site in the P-type ATPase and phosphatase members of the HAD (haloacid dehalogenase) superfamily by structural similarity to the response regulator protein CheY.
[12]
PubMed ID10449315
JournalCurr Opin Biotechnol
Year1999
Volume10
Pages365-9
AuthorsSwanson PE
TitleDehalogenases applied to industrial-scale biocatalysis.
[13]
CommentsX-ray crystallography
PubMed ID10521454
JournalJ Biol Chem
Year1999
Volume274
Pages30672-8
AuthorsRidder IS, Rozeboom HJ, Kalk KH, Dijkstra BW
TitleCrystal structures of intermediates in the dehalogenation of haloalkanoates by L-2-haloacid dehalogenase.
Related PDB1qq5,1qq6,1qq7
[14]
PubMed ID10485878
JournalProc Natl Acad Sci U S A
Year1999
Volume96
Pages10637-42
AuthorsArgiriadi MA, Morisseau C, Hammock BD, Christianson DW
TitleDetoxification of environmental mutagens and carcinogens: structure, mechanism, and evolution of liver epoxide hydrolase.
[15]
PubMed ID10919767
JournalAppl Environ Microbiol
Year2000
Volume66
Pages3180-6
AuthorsTsang JS, Pang BC
TitleIdentification of the dimerization domain of dehalogenase IVa of Burkholderia cepacia MBA4.
[16]
CommentsX-ray crystallography
PubMed ID11006296
JournalJ Biol Chem
Year2000
Volume275
Pages40804-9
AuthorsIchiyama S, Kurihara T, Li YF, Kogure Y, Tsunasawa S, Esaki N
TitleNovel catalytic mechanism of nucleophilic substitution by asparagine residue involving cyanoalanine intermediate revealed by mass spectrometric monitoring of an enzyme reaction.
Related PDB1qh9
[17]
PubMed ID11601995
JournalBiochemistry
Year2001
Volume40
Pages12704-11
AuthorsSelengut JD
TitleMDP-1 is a new and distinct member of the haloacid dehalogenase family of aspartate-dependent phosphohydrolases.
[18]
PubMed ID11404103
JournalCurr Opin Biotechnol
Year2001
Volume12
Pages254-8
AuthorsJanssen DB, Oppentocht JE, Poelarends GJ
TitleMicrobial dehalogenation.
[19]
PubMed ID15461449
JournalBiochemistry
Year2004
Volume43
Pages12770-9
AuthorsPeisach E, Selengut JD, Dunaway-Mariano D, Allen KN
TitleX-ray crystal structure of the hypothetical phosphotyrosine phosphatase MDP-1 of the haloacid dehalogenase superfamily.
[20]
PubMed ID14983068
JournalProtein Eng
Year2003
Volume16
Pages889-95
AuthorsStewart AJ, Schmid R, Blindauer CA, Paisey SJ, Farquharson C
TitleComparative modelling of human PHOSPHO1 reveals a new group of phosphatases within the haloacid dehalogenase superfamily.
[21]
PubMed ID14687572
JournalJ Mol Biol
Year2004
Volume335
Pages761-73
AuthorsCalderone V, Forleo C, Benvenuti M, Cristina Thaller M, Maria Rossolini G, Mangani S
TitleThe first structure of a bacterial class B Acid phosphatase reveals further structural heterogeneity among phosphatases of the haloacid dehalogenase fold.

comments
According to the literature [8], [10] & [13], the catalytic reaction proceeds as follows:
(1) Asp8 (of 1aq6) acts as a nucleophile, which makes a nucleophilic attack on the carbon, which is covalently bonded to halide atom, whereas Arg39 stabilizes and accepts the leaving halide atom. (The reaction proceeds via SN2 mechanism.)
(2) The intermediate is stabilized by an oxyanion hole, composed of Thr12/Ser173/Asn173 in the case of R=CH3 or larger alkyl group for the substrate, or Lys147 in the case of R=H for the substrate (see [10]). (substrate; R-CX-COOH)
(3) Lys147 and Tyr153 probably modulate the activity of Asp176, by lowering its pKa.
(4) Asp176 acts as a base, to activate a water. (The activated water might be stabilized by Asn173 (see [10] & [16].)
(5) The activated water makes a nucleophilic attack on the carbonyl carbon of Asp8-ligand intermediate, to complete the hydrolytic reaction.

createdupdated
2005-02-212009-02-26
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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