EzCatDB: S00176

DB codeS00176
RLCP classification5.10.68000.77
CATH domainDomain 13.10.450.50Catalytic domain
E.C.4.2.1.94
CSA1std

CATH domainRelated DB codes (homologues)
3.10.450.50S00545,S00177,T00024

Enzyme Name
Swiss-protKEGG

P56221
Protein nameScytalone dehydratasescytalone dehydratase
scytalone 7,8-hydro-lyase
SynonymsEC 4.2.1.94


Swiss-prot:Accession NumberP56221
Entry nameSCYD_MAGGR
ActivityScytalone = 1,3,8-trihydroxynaphthalene + H(2)O.
SubunitHomotrimer. Each subunit contains an active site, located in the central part of the hydrophobic core of the monomer, which functions independently.
Subcellular location
Cofactor


SubstratesProducts
KEGG-idC00779C01173C00001
CompoundScytalone1,3,8-TrihydroxynaphthaleneH2O
Typearomatic ring (only carbon atom),carbohydratearomatic ring (only carbon atom)H2O
1stdAAnalogue:BFSUnbound
2stdAAnalogue:CRPUnbound
3stdAUnboundAnalogue:MQ0
3stdBUnboundAnalogue:MQ0
3stdCUnboundAnalogue:MQ0
4stdAAnalogue:BFSUnbound
4stdBAnalogue:BFSUnbound
4stdCAnalogue:BFSUnbound
5stdAUnboundAnalogue:UNN
5stdBUnboundAnalogue:UNN
5stdCUnboundAnalogue:UNN
6stdAAnalogue:MS2Unbound
6stdBAnalogue:MS2Unbound
6stdCAnalogue:MS2Unbound
7stdAAnalogue:CRPUnbound
7stdBAnalogue:CRPUnbound
7stdCAnalogue:CRPUnbound

Active-site residues
resource
literature [2], [5], [7], [10], [11], [12]
pdbCatalytic residues
1stdATYR 30;ASP 31;TYR 50;HIS 85;HIS 110
2stdATYR 30;ASP 31;TYR 50;HIS 85;HIS 110
3stdATYR 30;ASP 31;TYR 50;HIS 85;HIS 110
3stdBTYR 30;ASP 31;TYR 50;HIS 85;HIS 110
3stdCTYR 30;ASP 31;TYR 50;HIS 85;HIS 110
4stdATYR 30;ASP 31;TYR 50;HIS 85;HIS 110
4stdBTYR 30;ASP 31;TYR 50;HIS 85;HIS 110
4stdCTYR 30;ASP 31;TYR 50;HIS 85;HIS 110
5stdATYR 30;ASP 31;TYR 50;HIS 85;HIS 110
5stdBTYR 30;ASP 31;TYR 50;HIS 85;HIS 110
5stdCTYR 30;ASP 31;TYR 50;HIS 85;HIS 110
6stdATYR 30;ASP 31;TYR 50;HIS 85;HIS 110
6stdBTYR 30;ASP 31;TYR 50;HIS 85;HIS 110
6stdCTYR 30;ASP 31;TYR 50;HIS 85;HIS 110
7stdATYR 30;ASP 31;TYR 50;HIS 85;HIS 110
7stdBTYR 30;ASP 31;TYR 50;HIS 85;HIS 110
7stdCTYR 30;ASP 31;TYR 50;HIS 85;HIS 110

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]Fig.10, p.940-9422
[7]Scheme 1p.6013
[10]p.431-432, p.438
[12]p.2281
[15]

[16]p.823-825

references
[1]
PubMed ID8355286
JournalJ Mol Biol
Year1993
Volume232
Pages999-1002
AuthorsLundqvist T, Weber PC, Hodge CN, Braswell EH, Rice J, Pierce J
TitlePreliminary crystallographic studies on scytalone dehydratase from Magnaporthe grisea.
[2]
CommentsX-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
Medline ID95171111
PubMed ID7866745
JournalStructure
Year1994
Volume2
Pages937-44
AuthorsLundqvist T, Rice J, Hodge CN, Basarab GS, Pierce J, Lindqvist Y
TitleCrystal structure of scytalone dehydratase--a disease determinant of the rice pathogen, Magnaporthe grisea.
Related PDB1std
Related Swiss-protP56221
[3]
PubMed ID8757804
JournalJ Mol Biol
Year1996
Volume260
Pages422-31
AuthorsBullock TL, Clarkson WD, Kent HM, Stewart M
TitleThe 1.6 angstroms resolution crystal structure of nuclear transport factor 2 (NTF2).
[4]
CommentsX-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
Medline ID99119201
PubMed ID9922139
JournalBiochemistry
Year1998
Volume37
Pages17735-44
AuthorsChen JM, Xu SL, Wawrzak Z, Basarab GS, Jordan DB
TitleStructure-based design of potent inhibitors of scytalone dehydratase: displacement of a water molecule from the active site.
Related PDB3std
Related Swiss-protP56221
[5]
CommentsX-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
Medline ID98332516
PubMed ID9665698
JournalBiochemistry
Year1998
Volume37
Pages9931-9
AuthorsNakasako M, Motoyama T, Kurahashi Y, Yamaguchi I
TitleCryogenic X-ray crystal structure analysis for the complex of scytalone dehydratase of a rice blast fungus and its tight-binding inhibitor, carpropamid: the structural basis of tight-binding inhibition.
Related PDB2std
Related Swiss-protP56221
[6]
PubMed ID10512727
JournalBiochem Biophys Res Commun
Year1999
Volume263
Pages617-20
AuthorsBasarab GS, Jordan DB
TitleWild-type enzyme as a reporter of inhibitor binding by catalytically impaired mutant enzymes.
[7]
PubMed ID10320327
JournalBiochemistry
Year1999
Volume38
Pages6012-24
AuthorsBasarab GS, Steffens JJ, Wawrzak Z, Schwartz RS, Lundqvist T, Jordan DB
TitleCatalytic mechanism of scytalone dehydratase: site-directed mutagenisis, kinetic isotope effects, and alternate substrates.
[8]
PubMed ID10386946
JournalBioorg Med Chem Lett
Year1999
Volume9
Pages1613-8
AuthorsBasarab GS, Jordan DB, Gehret TC, Schwartz RS, Wawrzak Z
TitleDesign of scytalone dehydratase inhibitors as rice blast fungicides: derivatives of norephedrine.
[9]
PubMed ID10386945
JournalBioorg Med Chem Lett
Year1999
Volume9
Pages1607-12
AuthorsJordan DB, Lessen TA, Wawrzak Z, Bisaha JJ, Gehret TC, Hansen SL, Schwartz RS, Basarab GS
TitleDesign of scytalone dehydratase inhibitors as rice blast fungicides: (N-phenoxypropyl)-carboxamides.
[10]
CommentsX-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS).
Medline ID99310043
PubMed ID10382670
JournalProteins
Year1999
Volume35
Pages425-39
AuthorsWawrzak Z, Sandalova T, Steffens JJ, Basarab GS, Lundqvist T, Lindqvist Y, Jordan DB
TitleHigh-resolution structures of scytalone dehydratase-inhibitor complexes crystallized at physiological pH.
Related PDB4std,5std,6std,7std
Related Swiss-protP56221
[11]
PubMed ID10913266
JournalBiochemistry
Year2000
Volume39
Pages8593-602
AuthorsJordan DB, Basarab GS, Steffens JJ, Schwartz RS, Doughty JG
TitleTight binding inhibitors of scytalone dehydratase: effects of site-directed mutations.
[12]
PubMed ID10694394
JournalBiochemistry
Year2000
Volume39
Pages2276-82
AuthorsJordan DB, Zheng YJ, Lockett BA, Basarab GS
TitleStereochemistry of the enolization of scytalone by scytalone dehydratase.
[13]
PubMed ID10882002
JournalBioorg Med Chem
Year2000
Volume8
Pages897-907
AuthorsJennings LD, Rayner DR, Jordan DB, Okonya JF, Basarab GS, Amorose DK, Anaclerio BM, Lee JK, Schwartz RS, Whitmore KA
TitleCyclobutane carboxamide inhibitors of fungal melanin: biosynthesis and their evaluation as fungicides.
[14]
PubMed ID10636235
JournalBioorg Med Chem Lett
Year2000
Volume10
Pages23-6
AuthorsJordan DB, Basarab GS
TitleBinding dynamics of two water molecules constrained within the scytalone dehydratase binding pocket.
[15]
PubMed ID10841474
JournalOrg Lett
Year2000
Volume2
Pages1541-4
AuthorsBasarab GS, Jordan DB, Zheng YJ
TitleSolvolytic enolization of scytalone.
[16]
PubMed ID11790103
JournalBiochemistry
Year2002
Volume41
Pages820-6
AuthorsZheng YJ, Basarab GS, Jordan DB
TitleRoles of substrate distortion and intramolecular hydrogen bonding in enzymatic catalysis by scytalone dehydratase.

comments
According to the literature [2], [7], [10] & [12], this enzyme catalyzes beta-elimination of water from the substrate through an E1cb-like mechanism. At the active site, His85 and Asp31 form a typical catalytic dyad, so that His85 acts as a general base. His85 and His110 seem to be bound to the product water molecule. Moreover, another water molecule, which is bound to the sidechains of Tyr30 and Tyr50, seems to act as a general acid-base.
Taken together, this enzyme catalyzes the following reactions:
(A) Elimination of hydroxyl group;
(A1) His85 abstract a proton (at the pro-R position) from the C2 atom of the substrate, leading to the formation of an enol intermediate. The formation of enol intermediate is assisted by the protonation to the carbonyl oxygen from the water bound to Tyr30 and Tyr50. During the reaction, His110 stabilizes the hydroxyl group at the C3 atom (beta-position).
(A2) His85 protonates the hydroxyl group at the C3 atom (beta-position), releasing a water from the substrate and forming a double bond between the C2 and C3 atom. This reaction is also assisted by the water bound to Tyr30 and Tyr50, which now acts as a general base to deprotonate the hydroxyl group of the enol intermediate.
(B) Isomerization (change in the position of double-bond);
(B1) Abstraction of a C4 proton and subsequent aromatization probably occurs spontaneously, by a tautomerization, to complete the reaction, according to the literature [2].

createdupdated
2004-06-212009-03-17
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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