EzCatDB: S00356

DB codeS00356
RLCP classification1.20.30810.950
CATH domainDomain 13.40.50.1820Catalytic domain
E.C.3.8.1.5
CSA1b6g

CATH domainRelated DB codes (homologues)
3.40.50.1820S00544,S00344,S00517,S00525,S00526,S00720,S00723,S00724,S00725,S00919,S00057,S00374,S00345,S00347,S00348,S00346,S00350,S00352,S00353,S00355,S00358,D00189,D00210,D00539,T00253

Enzyme Name
Swiss-protKEGG

P22643
Protein nameHaloalkane dehalogenasehaloalkane dehalogenase
1-chlorohexane halidohydrolase
1-haloalkane dehalogenase
SynonymsEC 3.8.1.5

KEGG pathways
MAP codePathways
MAP00361gamma-Hexachlorocyclohexane degradation
MAP00626Naphthalene and anthracene degradation
MAP006311,2-Dichloroethane degradation
MAP006413-Chloroacrylic acid degradation

Swiss-prot:Accession NumberP22643
Entry nameDHLA_XANAU
Activity1-haloalkane + H(2)O = a primary alcohol + halide.,1,2-dichloroethane + H(2)O = 2-chloroethanol + hydrogen chloride.
SubunitMonomer.
Subcellular location
Cofactor


SubstratesProductsintermediates
KEGG-idC01872C00001C01813C01706C00226C00462
Compound1-HaloalkaneH2OHaloalcoholHaloalkenePrimary alcoholHalide
TypehalideH2Ocarbohydrate,halidehalidecarbohydratehalide
1b6gAUnbound
UnboundUnboundUnboundBound:_CL 1998Unbound
1be0AUnbound
UnboundUnboundUnboundUnboundUnbound
1beeAUnbound
UnboundUnboundUnboundUnboundUnbound
1bezAUnbound
UnboundUnboundUnboundUnboundUnbound
1cijAUnbound
UnboundUnboundUnboundBound:_BR 401Unbound
1edbAUnbound
UnboundUnboundUnboundBound:_CLUnbound
1eddAUnbound
UnboundUnboundUnboundBound:_CLUnbound
1edeAUnbound
UnboundUnboundUnboundUnboundUnbound
1hdeAUnbound
UnboundUnboundUnboundUnboundUnbound
1hdeBUnbound
UnboundUnboundUnboundUnboundUnbound
2dhcABound:DCE
UnboundUnboundUnboundUnboundUnbound
2dhdAUnbound
UnboundUnboundUnboundBound:_CL 552Bound:MCE
2dheAUnbound
UnboundUnboundUnboundBound:_CLUnbound
2edaAUnbound
UnboundUnboundUnboundBound:IODUnbound
2edcAUnbound
UnboundUnboundUnboundBound:IODUnbound
2hadAUnbound
UnboundUnboundUnboundUnboundUnbound

Active-site residues
pdbCatalytic residuesMain-chain involved in catalysiscomment
1b6gAASP 124;ASP 260;HIS 289;TRP 125;TRP 175
GLU 56;TRP 125

1be0AASP 124;ASP 260;HIS 289;TRP 125;TRP 175
GLU 56;TRP 125
mutant I2V
1beeAASP 124;ASP 260;HIS 289;TRP 125;       
GLU 56;TRP 125
mutant I2V, W175Y
1bezAASP 124;ASP 260;HIS 289;TRP 125;       
GLU 56;TRP 125
mutant I2V, W175Y
1cijAASP 124;ASP 260;HIS 289;TRP 125;TRP 175
GLU 56;TRP 125
mutant I2V
1edbAASP 124;ASP 260;HIS 289;TRP 125;TRP 175
GLU 56;TRP 125

1eddAASP 124;ASP 260;HIS 289;TRP 125;TRP 175
GLU 56;TRP 125

1edeAASP 124;ASP 260;HIS 289;TRP 125;TRP 175
GLU 56;TRP 125

1hdeAASP 124;ASP 260;HIS 289;TRP 125;TRP 175
GLU 56;TRP 125
mutant F172W
1hdeBASP 124;ASP 260;HIS 289;TRP 125;TRP 175
GLU 56;TRP 125
mutant F172W
2dhcAASP 124;ASP 260;HIS 289;TRP 125;TRP 175
GLU 56;TRP 125

2dhdAASP 124;ASP 260;HIS 289;TRP 125;TRP 175
GLU 56;TRP 125

2dheAASP 124;ASP 260;HIS 289;TRP 125;TRP 175
GLU 56;TRP 125

2edaAASP 124;ASP 260;HIS 289;TRP 125;TRP 175
GLU 56;TRP 125

2edcAASP 124;ASP 260;HIS 289;TRP 125;TRP 175
GLU 56;TRP 125

2hadAASP 124;ASP 260;HIS 289;TRP 125;TRP 175
GLU 56;TRP 125


References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.1300
[2]Fig.12
[4]Fig.44
[10]p.995-996

references
[1]
CommentsX-ray crystallography (2.4 Angstroms)
Medline ID91224078
PubMed ID2026135
JournalEMBO J
Year1991
Volume10
Pages1297-1302
AuthorsFranken S.M., Rozeboom H.J., Kalk K.H., Dijkstra B.W
TitleCrystal structure of haloalkane dehalogenase: an enzyme to detoxify halogenated alkanes.
Related PDB2had
[2]
CommentsX-ray crystallography, catalysis
PubMed ID8369276
JournalBiochemistry
Year1993
Volume32
Pages9031-7
AuthorsVerschueren KH, Kingma J, Rozeboom HJ, Kalk KH, Janssen DB, Dijkstra BW
TitleCrystallographic and fluorescence studies of the interaction of haloalkane dehalogenase with halide ions. Studies with halide compounds reveal a halide binding site in the active site.
Related PDB1edb,1edd,2eda,2edc
[3]
CommentsX-ray crystallography (1.9 Angstroms)
PubMed ID8355275
JournalJ Mol Biol
Year1993
Volume232
Pages856-72
AuthorsVerschueren KH, Franken SM, Rozeboom HJ, Kalk KH, Dijkstra BW
TitleRefined X-ray structures of haloalkane dehalogenase at pH 6.2 and pH 8.2 and implications for the reaction mechanism.
Related PDB1ede
[4]
CommentsX-ray crystallography (2.4 Angstroms)
Medline ID93295480
PubMed ID8515812
JournalNature
Year1993
Volume363
Pages693-8
AuthorsVerschueren K.H.G., Seljee F., Rozeboom H.J., Kalk K.H., Dijkstra B.W
TitleCrystallographic analysis of the catalytic mechanism of haloalkane dehalogenase.
Related PDB2dhc,2dhd,2dhe
[5]
Commentscatalysis, X-ray crystallography
PubMed ID8855957
JournalBiochemistry
Year1996
Volume35
Pages13186-95
AuthorsSchanstra JP, Ridder IS, Heimeriks GJ, Rink R, Poelarends GJ, Kalk KH, Dijkstra BW, Janssen DB
TitleKinetic characterization and X-ray structure of a mutant of haloalkane dehalogenase with higher catalytic activity and modified substrate range.
Related PDB1hde
[6]
CommentsX-ray crystallography (1.96 Angstroms)
Medline ID99007117
PubMed ID9790663
JournalBiochemistry
Year1998
Volume37
Pages15013-23
AuthorsKrooshof G.H., Ridder I.S., Tepper A.W.J.W., Vos G.J., Rozeboom H.J., Kalk K.H., Dijkstra B.W., Janssen D.B
TitleKinetic analysis and X-ray structure of haloalkane dehalogenase with a modified halide-binding site.
Related PDB1bee,1bez
[7]
CommentsX-ray crystallography (1.15 Angstroms)
PubMed ID10393294
JournalActa Crystallogr D Biol Crystallogr
Year1999
Volume55
Pages1273-90
AuthorsRidder IS, Rozeboom HJ, Dijkstra BW
TitleHaloalkane dehalogenase from Xanthobacter autotrophicus GJ10 refined at 1.15 A resolution
Related PDB1b6g
[8]
CommentsX-ray crystallography (2.3 Angstroms)
Medline ID99438358
PubMed ID10508409
JournalBiochemistry
Year1999
Volume38
Pages12052-61
AuthorsPikkemaat M.G., Ridder I.S., Rozeboom H.J., Kalk K.H., Dijkstra B.W., Janssen D.B
TitleCrystallographic and kinetic evidence of a collision complex formed during halide import in haloalkane dehalogenase.
Related PDB1cij
[9]
CommentsX-ray crystallography (1.5 Angstroms)
PubMed ID10587433
JournalBiochemistry
Year1999
Volume38
Pages16105-14
AuthorsNewman J, Peat TS, Richard R, Kan L, Swanson PE, Affholter JA, Holmes IH, Schindler JF, Unkefer CJ, Terwilliger TC
TitleHaloalkane dehalogenases: structure of a Rhodococcus enzyme.
Related PDB1bn6,1bn7,1cqw
[10]
Commentsreaction mechanism and substrate specificity (comparative study)
PubMed ID10585505
JournalProtein Eng
Year1999
Volume12
Pages989-98
AuthorsDamborsky J, Koca J
TitleAnalysis of the reaction mechanism and substrate specificity of haloalkane dehalogenases by sequential and structural comparisons.
[11]
CommentsX-ray crystallography (1.58 Angstroms)
PubMed ID11087355
JournalBiochemistry
Year2000
Volume39
Pages14082-6
AuthorsMarek J, Vevodova J, Smatanova IK, Nagata Y, Svensson LA, Newman J, Takagi M, Damborsky J
TitleCrystal structure of the haloalkane dehalogenase from Sphingomonas paucimobilis UT26.
Related PDB1cv2,1d07
[12]
Commentscatalysis (mutatition analysis)
PubMed ID10850790
JournalJ Chem Inf Comput Sci
Year2000
Volume40
Pages839-46
AuthorsRobert D, Girones X, Carbo-Dorca R
TitleQuantification of the influence of single-point mutations on haloalkane dehalogenase activity: a molecular quantum similarity study.
[13]
Commentscatalysis
PubMed ID10963662
JournalProc Natl Acad Sci U S A
Year2000
Volume97
Pages9937-42
AuthorsLau EY, Kahn K, Bash PA, Bruice TC
TitleThe importance of reactant positioning in enzyme catalysis: a hybrid quantum mechanics/molecular mechanics study of a haloalkane dehalogenase.
[14]
Commentscatalysis (Erratum in:Biochemistry 2001 Sep 18;40(37):11288)
PubMed ID11467952
JournalBiochemistry
Year2001
Volume40
Pages8905-17
AuthorsKmunicek J, Luengo S, Gago F, Ortiz AR, Wade RC, Damborsky J
TitleComparative binding energy analysis of the substrate specificity of haloalkane dehalogenase from Xanthobacter autotrophicus GJ10.
[15]
Commentsmultiple computer-automated structure evaluation
PubMed ID11764149
JournalEnviron Toxicol Chem
Year2001
Volume20
Pages2681-9
AuthorsDamborsky J, Rorije E, Jesenska A, Nagata Y, Klopman G, Peijnenburg WJ
TitleStructure-specificity relationships for haloalkane dehalogenases.

comments
This enzyme belongs to haloalkane dehydrogenase Type-1 subfamily.
According to the literature [1], [2] & [4], the catalytic mechanism of this enzyme is very similar to that of trypsin (D00197 in EzCatDB), except for the fact that the reaction is assisted by the stabilizer for the leaving halide atom, Trp125 and Trp175. The reaction proceeds as follows:
(1) Asp124 acts as a nucleophile, which makes a nucleophilic attack on the C1 carbon of the substrate, to form a covalently bound ester inetermediate. In the meantime, slightly positively charged NH atoms of Trp125 and Trp175 stabilizes the leaving halogen atom, facilitating the reaction. (SN2-like mechanism) The transition state is stabilized by the mainchain amide groups of Glu56 and Trp125.
(2) The tetrahedral intermediate is formed, which is stabilized by the mainchain amide groups of Glu56 and Trp125.
(3) His289 acts as a general base to activate a water. (Asp260 modulates the activity of His289.)
(4) The activated water makes a nucleophilic attack on the intermediate, to complete the raction.
###
The data for the type-2 subfamily is deposited in S00525 of EzCatDB.

createdupdated
2002-09-052009-03-16


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)

© Computational Biology Research Center, AIST, 2004 All Rights Reserved.