S00176
type: Enzyme
rlcp: p77
cath: Nuclear Transport Factor 2; Chain
ec: https://purl.uniprot.org/enzyme/4.2.1.94
csa: 1std
uniprot: P56221
kegg enzyme: scytalone dehydratase
kegg enzyme: scytalone 7,8-hydro-lyase
kegg substrate: Scytalone
kegg product: 1,3,8-Trihydroxynaphthalene
kegg product: H2O
pdb: 1stdA
pdb: 2stdA
pdb: 3stdA
pdb: 3stdB
pdb: 3stdC
pdb: 4stdA
pdb: 4stdB
pdb: 4stdC
pdb: 5stdA
pdb: 5stdB
pdb: 5stdC
pdb: 6stdA
pdb: 6stdB
pdb: 6stdC
pdb: 7stdA
pdb: 7stdB
pdb: 7stdC
pdb bound state: Analogue
  compound: Scytalone
  pdb: 1stdA
  ligand het code: BFS
pdb bound state: Analogue
  compound: Scytalone
  pdb: 2stdA
  ligand het code: CRP
pdb bound state: Unbound
  compound: Scytalone
  pdb: 3stdA
pdb bound state: Unbound
  compound: Scytalone
  pdb: 3stdB
pdb bound state: Unbound
  compound: Scytalone
  pdb: 3stdC
pdb bound state: Analogue
  compound: Scytalone
  pdb: 4stdA
  ligand het code: BFS
pdb bound state: Analogue
  compound: Scytalone
  pdb: 4stdB
  ligand het code: BFS
pdb bound state: Analogue
  compound: Scytalone
  pdb: 4stdC
  ligand het code: BFS
pdb bound state: Unbound
  compound: Scytalone
  pdb: 5stdA
pdb bound state: Unbound
  compound: Scytalone
  pdb: 5stdB
pdb bound state: Unbound
  compound: Scytalone
  pdb: 5stdC
pdb bound state: Analogue
  compound: Scytalone
  pdb: 6stdA
  ligand het code: MS2
pdb bound state: Analogue
  compound: Scytalone
  pdb: 6stdB
  ligand het code: MS2
pdb bound state: Analogue
  compound: Scytalone
  pdb: 6stdC
  ligand het code: MS2
pdb bound state: Analogue
  compound: Scytalone
  pdb: 7stdA
  ligand het code: CRP
pdb bound state: Analogue
  compound: Scytalone
  pdb: 7stdB
  ligand het code: CRP
pdb bound state: Analogue
  compound: Scytalone
  pdb: 7stdC
  ligand het code: CRP
pdb bound state: Unbound
  compound: 1,3,8-Trihydroxynaphthalene
  pdb: 1stdA
pdb bound state: Unbound
  compound: 1,3,8-Trihydroxynaphthalene
  pdb: 2stdA
pdb bound state: Analogue
  compound: 1,3,8-Trihydroxynaphthalene
  pdb: 3stdA
  ligand het code: MQ0
pdb bound state: Analogue
  compound: 1,3,8-Trihydroxynaphthalene
  pdb: 3stdB
  ligand het code: MQ0
pdb bound state: Analogue
  compound: 1,3,8-Trihydroxynaphthalene
  pdb: 3stdC
  ligand het code: MQ0
pdb bound state: Unbound
  compound: 1,3,8-Trihydroxynaphthalene
  pdb: 4stdA
pdb bound state: Unbound
  compound: 1,3,8-Trihydroxynaphthalene
  pdb: 4stdB
pdb bound state: Unbound
  compound: 1,3,8-Trihydroxynaphthalene
  pdb: 4stdC
pdb bound state: Analogue
  compound: 1,3,8-Trihydroxynaphthalene
  pdb: 5stdA
  ligand het code: UNN
pdb bound state: Analogue
  compound: 1,3,8-Trihydroxynaphthalene
  pdb: 5stdB
  ligand het code: UNN
pdb bound state: Analogue
  compound: 1,3,8-Trihydroxynaphthalene
  pdb: 5stdC
  ligand het code: UNN
pdb bound state: Unbound
  compound: 1,3,8-Trihydroxynaphthalene
  pdb: 6stdA
active site residues resources: The 1.6 angstroms resolution crystal structure of nuclear transport factor 2 (NTF2).
active site residues resources: Wild-type enzyme as a reporter of inhibitor binding by catalytically impaired mutant enzymes.
active site residues resources: Design of scytalone dehydratase inhibitors as rice blast fungicides: derivatives of norephedrine.
active site residues resources: Tight binding inhibitors of scytalone dehydratase: effects of site-directed mutations.
active site residues resources: Stereochemistry of the enolization of scytalone by scytalone dehydratase.
active site residues resources: Cyclobutane carboxamide inhibitors of fungal melanin: biosynthesis and their evaluation as fungicides.
references: Preliminary crystallographic studies on scytalone dehydratase from Magnaporthe grisea.
references: Crystal structure of scytalone dehydratase--a disease determinant of the rice pathogen, Magnaporthe grisea.
references: The 1.6 angstroms resolution crystal structure of nuclear transport factor 2 (NTF2).
references: Structure-based design of potent inhibitors of scytalone dehydratase: displacement of a water molecule from the active site.
references: http://ezcatdb.cbrc.jp/EzCatDB/reference/S00176#5
references: Wild-type enzyme as a reporter of inhibitor binding by catalytically impaired mutant enzymes.
references: Catalytic mechanism of scytalone dehydratase: site-directed mutagenisis, kinetic isotope effects, and alternate substrates.
references: Design of scytalone dehydratase inhibitors as rice blast fungicides: derivatives of norephedrine.
references: Design of scytalone dehydratase inhibitors as rice blast fungicides: (N-phenoxypropyl)-carboxamides.
references: High-resolution structures of scytalone dehydratase-inhibitor complexes crystallized at physiological pH.
references: Tight binding inhibitors of scytalone dehydratase: effects of site-directed mutations.
references: Stereochemistry of the enolization of scytalone by scytalone dehydratase.
references: Cyclobutane carboxamide inhibitors of fungal melanin: biosynthesis and their evaluation as fungicides.
references: Binding dynamics of two water molecules constrained within the scytalone dehydratase binding pocket.
references: Solvolytic enolization of scytalone.
references: Roles of substrate distortion and intramolecular hydrogen bonding in enzymatic catalysis by scytalone dehydratase.
comment: 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].

Nuclear Transport Factor 2; Chain
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.10.450.50
catalytic domain: index.html

Scytalone
type: KeggSubstrate
references: KEGG:C00779
compound type: aromatic ring (only carbon atom)
compound type: carbohydrate
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

1,3,8-Trihydroxynaphthalene
type: KeggProduct
references: KEGG:C01173
compound type: aromatic ring (only carbon atom)
references: CHEBI:18393
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

H2O
type: KeggProduct
references: KEGG:C00001
compound type: H2O
references: CHEBI:15377
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

1stdA
type: Pdb
references: 1std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

2stdA
type: Pdb
references: 2std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

3stdA
type: Pdb
references: 3std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

3stdB
type: Pdb
references: 3std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

3stdC
type: Pdb
references: 3std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

4stdA
type: Pdb
references: 4std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:4std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

4stdB
type: Pdb
references: 4std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:4std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

4stdC
type: Pdb
references: 4std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:4std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

5stdA
type: Pdb
references: 5std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:5std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

5stdB
type: Pdb
references: 5std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:5std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

5stdC
type: Pdb
references: 5std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:5std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

6stdA
type: Pdb
references: 6std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:6std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

6stdB
type: Pdb
references: 6std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:6std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

6stdC
type: Pdb
references: 6std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:6std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

7stdA
type: Pdb
references: 7std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:7std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

7stdB
type: Pdb
references: 7std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:7std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

7stdC
type: Pdb
references: 7std
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:7std
catalytic residue: TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

Preliminary crystallographic studies on scytalone dehydratase from Magnaporthe grisea.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8355286
journal: J Mol Biol
volume: 232
pages: 999-1002
published year: 1993
authors:
  item: Lundqvist T
  item: Weber PC
  item: Hodge CN
  item: Braswell EH
  item: Rice J
  item: Pierce J

Crystal structure of scytalone dehydratase--a disease determinant of the rice pathogen, Magnaporthe grisea.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
medline id: 95171111
references: http://www.ncbi.nlm.nih.gov/pubmed/7866745
journal: Structure
volume: 2
pages: 937-44
published year: 1994
authors:
  item: Lundqvist T
  item: Rice J
  item: Hodge CN
  item: Basarab GS
  item: Pierce J
  item: Lindqvist Y
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P56221

The 1.6 angstroms resolution crystal structure of nuclear transport factor 2 (NTF2).
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8757804
journal: J Mol Biol
volume: 260
pages: 422-31
published year: 1996
authors:
  item: Bullock TL
  item: Clarkson WD
  item: Kent HM
  item: Stewart M

Structure-based design of potent inhibitors of scytalone dehydratase: displacement of a water molecule from the active site.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
medline id: 99119201
references: http://www.ncbi.nlm.nih.gov/pubmed/9922139
journal: Biochemistry
volume: 37
pages: 17735-44
published year: 1998
authors:
  item: Chen JM
  item: Xu SL
  item: Wawrzak Z
  item: Basarab GS
  item: Jordan DB
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P56221

http://ezcatdb.cbrc.jp/EzCatDB/reference/S00176#5
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
medline id: 98332516
references: http://www.ncbi.nlm.nih.gov/pubmed/9665698
journal: Biochemistry
volume: 37
pages: 9931-9
published year: 1998
authors:
  item: Nakasako M
  item: Motoyama T
  item: Kurahashi Y
  item: Yamaguchi I
title: Cryogenic 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.
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P56221

Wild-type enzyme as a reporter of inhibitor binding by catalytically impaired mutant enzymes.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10512727
journal: Biochem Biophys Res Commun
volume: 263
pages: 617-20
published year: 1999
authors:
  item: Basarab GS
  item: Jordan DB

Catalytic mechanism of scytalone dehydratase: site-directed mutagenisis, kinetic isotope effects, and alternate substrates.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10320327
journal: Biochemistry
volume: 38
pages: 6012-24
published year: 1999
authors:
  item: Basarab GS
  item: Steffens JJ
  item: Wawrzak Z
  item: Schwartz RS
  item: Lundqvist T
  item: Jordan DB

Design of scytalone dehydratase inhibitors as rice blast fungicides: derivatives of norephedrine.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10386946
journal: Bioorg Med Chem Lett
volume: 9
pages: 1613-8
published year: 1999
authors:
  item: Basarab GS
  item: Jordan DB
  item: Gehret TC
  item: Schwartz RS
  item: Wawrzak Z

Design of scytalone dehydratase inhibitors as rice blast fungicides: (N-phenoxypropyl)-carboxamides.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10386945
journal: Bioorg Med Chem Lett
volume: 9
pages: 1607-12
published year: 1999
authors:
  item: Jordan DB
  item: Lessen TA
  item: Wawrzak Z
  item: Bisaha JJ
  item: Gehret TC
  item: Hansen SL
  item: Schwartz RS
  item: Basarab GS

High-resolution structures of scytalone dehydratase-inhibitor complexes crystallized at physiological pH.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS).
medline id: 99310043
references: http://www.ncbi.nlm.nih.gov/pubmed/10382670
journal: Proteins
volume: 35
pages: 425-39
published year: 1999
authors:
  item: Wawrzak Z
  item: Sandalova T
  item: Steffens JJ
  item: Basarab GS
  item: Lundqvist T
  item: Lindqvist Y
  item: Jordan DB
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P56221

Tight binding inhibitors of scytalone dehydratase: effects of site-directed mutations.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10913266
journal: Biochemistry
volume: 39
pages: 8593-602
published year: 2000
authors:
  item: Jordan DB
  item: Basarab GS
  item: Steffens JJ
  item: Schwartz RS
  item: Doughty JG

Stereochemistry of the enolization of scytalone by scytalone dehydratase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10694394
journal: Biochemistry
volume: 39
pages: 2276-82
published year: 2000
authors:
  item: Jordan DB
  item: Zheng YJ
  item: Lockett BA
  item: Basarab GS

Cyclobutane carboxamide inhibitors of fungal melanin: biosynthesis and their evaluation as fungicides.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10882002
journal: Bioorg Med Chem
volume: 8
pages: 897-907
published year: 2000
authors:
  item: Jennings LD
  item: Rayner DR
  item: Jordan DB
  item: Okonya JF
  item: Basarab GS
  item: Amorose DK
  item: Anaclerio BM
  item: Lee JK
  item: Schwartz RS
  item: Whitmore KA

Binding dynamics of two water molecules constrained within the scytalone dehydratase binding pocket.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10636235
journal: Bioorg Med Chem Lett
volume: 10
pages: 23-6
published year: 2000
authors:
  item: Jordan DB
  item: Basarab GS

Solvolytic enolization of scytalone.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10841474
journal: Org Lett
volume: 2
pages: 1541-4
published year: 2000
authors:
  item: Basarab GS
  item: Jordan DB
  item: Zheng YJ

Roles of substrate distortion and intramolecular hydrogen bonding in enzymatic catalysis by scytalone dehydratase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11790103
journal: Biochemistry
volume: 41
pages: 820-6
published year: 2002
authors:
  item: Zheng YJ
  item: Basarab GS
  item: Jordan DB

ReferenceForCatalyticMechanism
reference index: 2
reference section: Fig.10, p.940-942
reference step: 2

ReferenceForCatalyticMechanism
reference index: 7
reference section: Scheme 1
reference step: p.6013

ReferenceForCatalyticMechanism
reference index: 10
reference section: p.431-432, p.438

ReferenceForCatalyticMechanism
reference index: 12
reference section: p.2281

ReferenceForCatalyticMechanism
reference index: 15

ReferenceForCatalyticMechanism
reference index: 16
reference section: p.823-825