DB code: S00176

RLCP classification 5.10.68000.77 : Elimination
CATH domain 3.10.450.50 : Nuclear Transport Factor 2; Chain Catalytic domain
E.C. 4.2.1.94
CSA 1std
M-CSA 1std
MACiE

CATH domain Related DB codes (homologues)
3.10.450.50 : Nuclear Transport Factor 2; Chain S00545 S00177 T00024

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P56221 Scytalone dehydratase
EC 4.2.1.94
XP_003712572.1 (Protein)
XM_003712524.1 (DNA/RNA sequence)
PF02982 (Scytalone_dh)
[Graphical View]

KEGG enzyme name
scytalone dehydratase
scytalone 7,8-hydro-lyase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P56221 SCYD_MAGGR Scytalone = 1,3,8-trihydroxynaphthalene + H(2)O. Homotrimer. Each subunit contains an active site, located in the central part of the hydrophobic core of the monomer, which functions independently.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00779 C01173 C00001
E.C.
Compound Scytalone 1,3,8-Trihydroxynaphthalene H2O
Type aromatic ring (only carbon atom),carbohydrate aromatic ring (only carbon atom) H2O
ChEBI 18393
 18393
 		15377
 15377
PubChem 439309
 439309
 		439428
 439428
 		22247451
 962
 22247451
 962
1stdA Analogue:BFS Unbound
2stdA Analogue:CRP Unbound
3stdA Unbound Analogue:MQ0
3stdB Unbound Analogue:MQ0
3stdC Unbound Analogue:MQ0
4stdA Analogue:BFS Unbound
4stdB Analogue:BFS Unbound
4stdC Analogue:BFS Unbound
5stdA Unbound Analogue:UNN
5stdB Unbound Analogue:UNN
5stdC Unbound Analogue:UNN
6stdA Analogue:MS2 Unbound
6stdB Analogue:MS2 Unbound
6stdC Analogue:MS2 Unbound
7stdA Analogue:CRP Unbound
7stdB Analogue:CRP Unbound
7stdC Analogue:CRP Unbound

Reference for Active-site residues
resource references E.C.
literature [2], [5], [7], [10], [11], [12]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1stdA TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
2stdA TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
3stdA TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
3stdB TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
3stdC TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
4stdA TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
4stdB TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
4stdC TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
5stdA TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
5stdB TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
5stdC TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
6stdA TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
6stdB TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
6stdC TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
7stdA TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
7stdB TYR 30;ASP 31;TYR 50;HIS 85;HIS 110
7stdC TYR 30;ASP 31;TYR 50;HIS 85;HIS 110

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Fig.10, p.940-942 2
[7]
Scheme 1 p.6013
[10]
p.431-432, p.438
[12]
p.2281
[15]
[16]
p.823-825

References
[1]
Resource
Comments
Medline ID
PubMed ID 8355286
Journal J Mol Biol
Year 1993
Volume 232
Pages 999-1002
Authors Lundqvist T, Weber PC, Hodge CN, Braswell EH, Rice J, Pierce J
Title Preliminary crystallographic studies on scytalone dehydratase from Magnaporthe grisea.
Related PDB
Related UniProtKB
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
Medline ID 95171111
PubMed ID 7866745
Journal Structure
Year 1994
Volume 2
Pages 937-44
Authors Lundqvist T, Rice J, Hodge CN, Basarab GS, Pierce J, Lindqvist Y
Title Crystal structure of scytalone dehydratase--a disease determinant of the rice pathogen, Magnaporthe grisea.
Related PDB 1std
Related UniProtKB P56221
[3]
Resource
Comments
Medline ID
PubMed ID 8757804
Journal J Mol Biol
Year 1996
Volume 260
Pages 422-31
Authors Bullock TL, Clarkson WD, Kent HM, Stewart M
Title The 1.6 angstroms resolution crystal structure of nuclear transport factor 2 (NTF2).
Related PDB
Related UniProtKB
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
Medline ID 99119201
PubMed ID 9922139
Journal Biochemistry
Year 1998
Volume 37
Pages 17735-44
Authors Chen JM, Xu SL, Wawrzak Z, Basarab GS, Jordan DB
Title Structure-based design of potent inhibitors of scytalone dehydratase: displacement of a water molecule from the active site.
Related PDB 3std
Related UniProtKB P56221
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
Medline ID 98332516
PubMed ID 9665698
Journal Biochemistry
Year 1998
Volume 37
Pages 9931-9
Authors Nakasako M, Motoyama T, Kurahashi Y, 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.
Related PDB 2std
Related UniProtKB P56221
[6]
Resource
Comments
Medline ID
PubMed ID 10512727
Journal Biochem Biophys Res Commun
Year 1999
Volume 263
Pages 617-20
Authors Basarab GS, Jordan DB
Title Wild-type enzyme as a reporter of inhibitor binding by catalytically impaired mutant enzymes.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10320327
Journal Biochemistry
Year 1999
Volume 38
Pages 6012-24
Authors Basarab GS, Steffens JJ, Wawrzak Z, Schwartz RS, Lundqvist T, Jordan DB
Title Catalytic mechanism of scytalone dehydratase: site-directed mutagenisis, kinetic isotope effects, and alternate substrates.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10386946
Journal Bioorg Med Chem Lett
Year 1999
Volume 9
Pages 1613-8
Authors Basarab GS, Jordan DB, Gehret TC, Schwartz RS, Wawrzak Z
Title Design of scytalone dehydratase inhibitors as rice blast fungicides: derivatives of norephedrine.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10386945
Journal Bioorg Med Chem Lett
Year 1999
Volume 9
Pages 1607-12
Authors Jordan DB, Lessen TA, Wawrzak Z, Bisaha JJ, Gehret TC, Hansen SL, Schwartz RS, Basarab GS
Title Design of scytalone dehydratase inhibitors as rice blast fungicides: (N-phenoxypropyl)-carboxamides.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS).
Medline ID 99310043
PubMed ID 10382670
Journal Proteins
Year 1999
Volume 35
Pages 425-39
Authors Wawrzak Z, Sandalova T, Steffens JJ, Basarab GS, Lundqvist T, Lindqvist Y, Jordan DB
Title High-resolution structures of scytalone dehydratase-inhibitor complexes crystallized at physiological pH.
Related PDB 4std 5std 6std 7std
Related UniProtKB P56221
[11]
Resource
Comments
Medline ID
PubMed ID 10913266
Journal Biochemistry
Year 2000
Volume 39
Pages 8593-602
Authors Jordan DB, Basarab GS, Steffens JJ, Schwartz RS, Doughty JG
Title Tight binding inhibitors of scytalone dehydratase: effects of site-directed mutations.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 10694394
Journal Biochemistry
Year 2000
Volume 39
Pages 2276-82
Authors Jordan DB, Zheng YJ, Lockett BA, Basarab GS
Title Stereochemistry of the enolization of scytalone by scytalone dehydratase.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 10882002
Journal Bioorg Med Chem
Year 2000
Volume 8
Pages 897-907
Authors Jennings LD, Rayner DR, Jordan DB, Okonya JF, Basarab GS, Amorose DK, Anaclerio BM, Lee JK, Schwartz RS, Whitmore KA
Title Cyclobutane carboxamide inhibitors of fungal melanin: biosynthesis and their evaluation as fungicides.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 10636235
Journal Bioorg Med Chem Lett
Year 2000
Volume 10
Pages 23-6
Authors Jordan DB, Basarab GS
Title Binding dynamics of two water molecules constrained within the scytalone dehydratase binding pocket.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 10841474
Journal Org Lett
Year 2000
Volume 2
Pages 1541-4
Authors Basarab GS, Jordan DB, Zheng YJ
Title Solvolytic enolization of scytalone.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 11790103
Journal Biochemistry
Year 2002
Volume 41
Pages 820-6
Authors Zheng YJ, Basarab GS, Jordan DB
Title Roles of substrate distortion and intramolecular hydrogen bonding in enzymatic catalysis by scytalone dehydratase.
Related PDB
Related UniProtKB

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].

Created Updated
2004-06-21 2009-03-17