DB code: S00525

RLCP classification 1.20.30810.951 : Hydrolysis
CATH domain 3.40.50.1820 : Rossmann fold Catalytic domain
E.C. 3.8.1.5
CSA 1cv2
M-CSA 1cv2
MACiE

CATH domain Related DB codes (homologues)
3.40.50.1820 : Rossmann fold S00544 S00344 S00517 S00526 S00720 S00723 S00724 S00725 S00919 S00057 S00374 S00345 S00347 S00348 S00346 S00350 S00352 S00353 S00355 S00356 S00358 D00189 D00210 D00539 T00253

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS
P59336 Haloalkane dehalogenase
EC 3.8.1.5
S33.990 (Serine)
P51698 Haloalkane dehalogenase
EC 3.8.1.5
1,3,4,6-tetrachloro-1,4-cyclohexadiene hydrolase
1,4-TCDN chlorohydrolase

KEGG enzyme name
haloalkane dehalogenase
1-chlorohexane halidohydrolase
1-haloalkane dehalogenase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P59336 DHAA_RHOSD 1-haloalkane + H(2)O = a primary alcohol + halide. Monomer (By similarity).
P51698 LINB_PSEPA 1-haloalkane + H(2)O = a primary alcohol + halide. 1,4-TCDN + 2 H(2)O = 2,5-DDOL + 2 chloride. Monomer. Periplasm.

KEGG Pathways
Map code Pathways E.C.
MAP00361 gamma-Hexachlorocyclohexane degradation
MAP00626 Naphthalene and anthracene degradation
MAP00631 1,2-Dichloroethane degradation
MAP00641 3-Chloroacrylic acid degradation

Compound table
Substrates Products Intermediates
KEGG-id C01872 C00001 C01813 C01706 C00226 C00462
E.C.
Compound 1-Haloalkane H2O Haloalcohol Haloalkene Primary alcohol Halide
Type halide H2O carbohydrate,halide halide carbohydrate halide
ChEBI 15377
 15377
PubChem 22247451
 962
 22247451
 962
1bn6A Unbound Unbound Unbound Unbound Unbound
1bn7A Unbound Unbound Unbound Unbound Unbound
1cqwA Unbound Unbound Unbound Unbound Bound:IOD_321
1cv2A Unbound Unbound Unbound Unbound Unbound
1d07A Unbound Unbound Unbound Bound:PDO Bound:_BR_901
1g42A Bound:CP2 Unbound Unbound Unbound Bound:_CL_604
1g4hA Unbound Unbound Unbound Bound:1BO Bound:_CL
1g5fA Bound:DCE Unbound Unbound Unbound Bound:_CL
1iz7A Unbound Unbound Unbound Unbound Bound:_CL
1iz8A Unbound Unbound Unbound Bound:PDO Bound:_BR
1k5pA Unbound Unbound Unbound Unbound Bound:_CL_1001
1k63A Unbound Unbound Unbound Bound:BRP Bound:_BR_1001,_CL_1003
1k6eA Unbound Unbound Unbound Bound:PGO,1BP_2002 Bound:_BR_1001,_CL_1003
1mj5A Unbound Unbound Unbound Unbound Bound:_CL_2004

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1bn6A ASP 117;GLU 141;HIS 283;ASN 52;TRP 118 ASN 52;TRP 118
1bn7A ASP 117;GLU 141;HIS 283;ASN 52;TRP 118 ASN 52;TRP 118
1cqwA ASP 117;GLU 141;HIS 283;ASN 52;TRP 118 ASN 52;TRP 118
1cv2A ASP 108;GLU 132;HIS 272;ASN 38;TRP 109 ASN 38;TRP 109
1d07A ASP 108;GLU 132;HIS 272;ASN 38;TRP 109 ASN 38;TRP 109
1g42A ASP 108;GLU 132;HIS 272;ASN 38;TRP 109 ASN 38;TRP 109
1g4hA ASP 108;GLU 132;HIS 272;ASN 38;TRP 109 ASN 38;TRP 109
1g5fA ASP 108;GLU 132;HIS 272;ASN 38;TRP 109 ASN 38;TRP 109
1iz7A ASP 108;GLU 132;HIS 272;ASN 38;TRP 109 ASN 38;TRP 109
1iz8A ASP 108;GLU 132;HIS 272;ASN 38;TRP 109 ASN 38;TRP 109
1k5pA ASP 108;GLU 132;HIS 272;ASN 38;TRP 109 ASN 38;TRP 109
1k63A ASP 108;GLU 132;HIS 272;ASN 38;TRP 109 ASN 38;TRP 109
1k6eA ASP 108;GLU 132;HIS 272;ASN 38;TRP 109 ASN 38;TRP 109
1mj5A ASP 108;GLU 132;HIS 272;ASN 38;TRP 109 ASN 38;TRP 109

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.1300
[2]
Fig.1 2
[4]
Fig.4 4
[9]
p.16109-16110
[10]
p.995-996
[11]
p.14085

References
[1]
Resource
Comments X-ray crystallography (2.4 Angstroms)
Medline ID 91224078
PubMed ID 2026135
Journal EMBO J
Year 1991
Volume 10
Pages 1297-1302
Authors Franken S.M., Rozeboom H.J., Kalk K.H., Dijkstra B.W
Title Crystal structure of haloalkane dehalogenase: an enzyme to detoxify halogenated alkanes.
Related PDB 2had
Related UniProtKB
[2]
Resource
Comments X-ray crystallography, catalysis
Medline ID
PubMed ID 8369276
Journal Biochemistry
Year 1993
Volume 32
Pages 9031-7
Authors Verschueren KH, Kingma J, Rozeboom HJ, Kalk KH, Janssen DB, Dijkstra BW
Title Crystallographic 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 PDB 1edb 1edd 2eda 2edc
Related UniProtKB
[3]
Resource
Comments X-ray crystallography (1.9 Angstroms)
Medline ID
PubMed ID 8355275
Journal J Mol Biol
Year 1993
Volume 232
Pages 856-72
Authors Verschueren KH, Franken SM, Rozeboom HJ, Kalk KH, Dijkstra BW
Title Refined X-ray structures of haloalkane dehalogenase at pH 6.2 and pH 8.2 and implications for the reaction mechanism.
Related PDB 1ede
Related UniProtKB
[4]
Resource
Comments X-ray crystallography (2.4 Angstroms)
Medline ID 93295480
PubMed ID 8515812
Journal Nature
Year 1993
Volume 363
Pages 693-8
Authors Verschueren K.H.G., Seljee F., Rozeboom H.J., Kalk K.H., Dijkstra B.W
Title Crystallographic analysis of the catalytic mechanism of haloalkane dehalogenase.
Related PDB 2dhc 2dhd 2dhe
Related UniProtKB
[5]
Resource
Comments catalysis, X-ray crystallography
Medline ID
PubMed ID 8855957
Journal Biochemistry
Year 1996
Volume 35
Pages 13186-95
Authors Schanstra JP, Ridder IS, Heimeriks GJ, Rink R, Poelarends GJ, Kalk KH, Dijkstra BW, Janssen DB
Title Kinetic characterization and X-ray structure of a mutant of haloalkane dehalogenase with higher catalytic activity and modified substrate range.
Related PDB 1hde
Related UniProtKB
[6]
Resource
Comments X-ray crystallography (1.96 Angstroms)
Medline ID 99007117
PubMed ID 9790663
Journal Biochemistry
Year 1998
Volume 37
Pages 15013-23
Authors Krooshof 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
Title Kinetic analysis and X-ray structure of haloalkane dehalogenase with a modified halide-binding site.
Related PDB 1bee 1bez
Related UniProtKB
[7]
Resource
Comments X-ray crystallography (1.15 Angstroms)
Medline ID
PubMed ID 10393294
Journal Acta Crystallogr D Biol Crystallogr
Year 1999
Volume 55
Pages 1273-90
Authors Ridder IS, Rozeboom HJ, Dijkstra BW
Title Haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 refined at 1.15 A resolution
Related PDB 1b6g
Related UniProtKB
[8]
Resource
Comments X-ray crystallography (2.3 Angstroms)
Medline ID 99438358
PubMed ID 10508409
Journal Biochemistry
Year 1999
Volume 38
Pages 12052-61
Authors Pikkemaat M.G., Ridder I.S., Rozeboom H.J., Kalk K.H., Dijkstra B.W., Janssen D.B
Title Crystallographic and kinetic evidence of a collision complex formed during halide import in haloalkane dehalogenase.
Related PDB 1cijA
Related UniProtKB
[9]
Resource
Comments X-ray crystallography (1.5 Angstroms)
Medline ID
PubMed ID 10587433
Journal Biochemistry
Year 1999
Volume 38
Pages 16105-14
Authors Newman J, Peat TS, Richard R, Kan L, Swanson PE, Affholter JA, Holmes IH, Schindler JF, Unkefer CJ, Terwilliger TC
Title Haloalkane dehalogenases: structure of a Rhodococcus enzyme.
Related PDB 1bn6 1bn7 1cqw
Related UniProtKB
[10]
Resource
Comments reaction mechanism and substrate specificity (comparative study)
Medline ID
PubMed ID 10585505
Journal Protein Eng
Year 1999
Volume 12
Pages 989-98
Authors Damborsky J, Koca J
Title Analysis of the reaction mechanism and substrate specificity of haloalkane dehalogenases by sequential and structural comparisons.
Related PDB
Related UniProtKB
[11]
Resource
Comments X-ray crystallography (1.58 Angstroms)
Medline ID
PubMed ID 11087355
Journal Biochemistry
Year 2000
Volume 39
Pages 14082-6
Authors Marek J, Vevodova J, Smatanova IK, Nagata Y, Svensson LA, Newman J, Takagi M, Damborsky J
Title Crystal structure of the haloalkane dehalogenase from Sphingomonas paucimobilis UT26.
Related PDB 1cv2 1d07
Related UniProtKB
[12]
Resource
Comments catalysis (mutatition analysis)
Medline ID
PubMed ID 10850790
Journal J Chem Inf Comput Sci
Year 2000
Volume 40
Pages 839-46
Authors Robert D, Girones X, Carbo-Dorca R
Title Quantification of the influence of single-point mutations on haloalkane dehalogenase activity: a molecular quantum similarity study.
Related PDB
Related UniProtKB
[13]
Resource
Comments catalysis
Medline ID
PubMed ID 10963662
Journal Proc Natl Acad Sci U S A
Year 2000
Volume 97
Pages 9937-42
Authors Lau EY, Kahn K, Bash PA, Bruice TC
Title The importance of reactant positioning in enzyme catalysis: a hybrid quantum mechanics/molecular mechanics study of a haloalkane dehalogenase.
Related PDB
Related UniProtKB
[14]
Resource
Comments catalysis (Erratum in:Biochemistry 2001 Sep 18;40(37):11288)
Medline ID
PubMed ID 11467952
Journal Biochemistry
Year 2001
Volume 40
Pages 8905-17
Authors Kmunicek J, Luengo S, Gago F, Ortiz AR, Wade RC, Damborsky J
Title Comparative binding energy analysis of the substrate specificity of haloalkane dehalogenase from Xanthobacter autotrophicus GJ10.
Related PDB
Related UniProtKB
[15]
Resource
Comments multiple computer-automated structure evaluation
Medline ID
PubMed ID 11764149
Journal Environ Toxicol Chem
Year 2001
Volume 20
Pages 2681-9
Authors Damborsky J, Rorije E, Jesenska A, Nagata Y, Klopman G, Peijnenburg WJ
Title Structure-specificity relationships for haloalkane dehalogenases.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 11939779
Journal Biochemistry
Year 2002
Volume 41
Pages 4847-55
Authors Oakley AJ, Prokop Z, Bohac M, Kmunicek J, Jedlicka T, Monincova M, Kuta-Smatanova I, Nagata Y, Damborsky J, Wilce MC
Title Exploring the structure and activity of haloalkane dehalogenase from Sphingomonas paucimobilis UT26: evidence for product- and water-mediated inhibition.
Related PDB 1g42 1g4h 1g5f
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 12939138
Journal Biochemistry
Year 2003
Volume 42
Pages 10104-12
Authors Streltsov VA, Prokop Z, Damborsky J, Nagata Y, Oakley A, Wilce MC
Title Haloalkane dehalogenase LinB from Sphingomonas paucimobilis UT26: X-ray crystallographic studies of dehalogenation of brominated substrates.
Related PDB 1iz7 1iz8 1k5p 1k63 1k6e
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 14744129
Journal Biochemistry
Year 2004
Volume 43
Pages 870-8
Authors Oakley AJ, Klvana M, Otyepka M, Nagata Y, Wilce MC, Damborsky J
Title Crystal structure of haloalkane dehalogenase LinB from Sphingomonas paucimobilis UT26 at 0.95 A resolution: dynamics of catalytic residues.
Related PDB 1mj5
Related UniProtKB

Comments
This enzyme belongs to haloalkane dehydrogenase Type-2 subfamily. The enzyme data for the type-1 subfamily is deposited in S00356 of EzCatDB.
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, Asn52 and Trp118 (of 1bn6). The reaction proceeds as follows:
(1) Asp117 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, sidechain atoms of Asn52 and Trp118 stabilizes the leaving halogen atom, facilitating the reaction. (SN2-like mechanism) The transition state is stabilized by the mainchain amide groups of Asn52 and Trp118.
(2) The tetrahedral intermediate is formed, which is stabilized by the mainchain amide groups of Asn52 and Trp118.
(3) His272 acts as a general base to activate a water. (Glu132 modulates the activity of His272.)
(4) The activated water makes a nucleophilic attack on the intermediate, to complete the reaction.

Created Updated
2003-06-27 2009-03-17