DB code: S00336

RLCP classification 9.5010.536200.8010 : Hydride transfer
CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
E.C. 1.1.1.252
CSA 1ybv
M-CSA 1ybv
MACiE

CATH domain Related DB codes (homologues)
3.40.50.720 : Rossmann fold S00543 S00551 S00552 S00553 S00602 S00604 S00605 S00608 S00610 S00625 S00319 S00328 S00329 S00330 S00331 S00332 D00456 D00457 D00458 S00324 S00320 S00325 S00326 S00327 D00459 S00335 S00334 T00219 S00339 D00513 D00001 D00002 D00003 D00005 D00007 D00008 D00010 D00012 D00017 D00018 D00023 D00027 D00028 D00031 D00032 D00033 D00034 D00035 D00037 D00048 D00071 D00476 D00481 D00482 D00490 D00492 D00494 D00545 D00601 D00603 D00604 D00605 D00615 D00845 D00857 D00858 M00161 M00171 M00210 T00002 T00010 T00011 T00015 T00227 T00247 T00408 T00414 D00827 D00262 D00274 D00275 M00035 T00109

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q12634 Tetrahydroxynaphthalene reductase
EC 1.1.1.252
T4HN reductase
THNR
XP_003709023.1 (Protein)
XM_003708975.1 (DNA/RNA sequence)
PF00106 (adh_short)
[Graphical View]

KEGG enzyme name
tetrahydroxynaphthalene reductase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q12634 T4HR_MAGGR Scytalone + NADP(+) = 1,3,6,8- tetrahydroxynaphthalene + NADPH. Homotetramer.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C04033 C00005 C00080 C00779 C00006 I00095
E.C.
Compound 1,3,6,8-Tetrahydroxynaphthalene NADPH H+ scytalone NADP 3-oxo-1,6,8-trihydroxynaphthalene
Type aromatic ring (only carbon atom) amide group,amine group,nucleotide others aromatic ring (only carbon atom),carbohydrate amide group,amine group,nucleotide
ChEBI 18365
16474
15378
18009
PubChem 440202
5884
1038
439309
5886
1ybvA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:NDP Unbound Unbound Intermediate-analogue:BEA
1ybvB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:NDP Unbound Unbound Intermediate-analogue:BEA
1dohA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:NDP Unbound Unbound Intermediate-analogue:NID
1dohB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:NDP Unbound Unbound Intermediate-analogue:NID
1g0nA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:PHH Bound:NDP Unbound Unbound Unbound
1g0nB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:NDP Unbound Unbound Unbound
1g0oA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:NDP Unbound Unbound Intermediate-analogue:PYQ
1g0oB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:NDP Unbound Unbound Intermediate-analogue:PYQ
1g0oC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:NDP Unbound Unbound Intermediate-analogue:PYQ
1g0oD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:NDP Unbound Unbound Intermediate-analogue:PYQ

Reference for Active-site residues
resource references E.C.
literature [9]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ybvA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 164;TYR 178;LYS 182;TYR 223 mutant P2A,S241V,A242Q,H247R
1ybvB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 164;TYR 178;LYS 182;TYR 223 mutant P2A,S241V,A242Q,H247R
1dohA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 164;TYR 178;LYS 182;TYR 223
1dohB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 164;TYR 178;LYS 182;TYR 223
1g0nA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 164;TYR 178;LYS 182;TYR 223
1g0nB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 164;TYR 178;LYS 182; invisible 219-235
1g0oA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 164;TYR 178;LYS 182;TYR 223
1g0oB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 164;TYR 178;LYS 182;TYR 223
1g0oC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 164;TYR 178;LYS 182;TYR 223
1g0oD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 164;TYR 178;LYS 182;TYR 223

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
p.1167-1168
[3]
Fig.3, Fig.6, p.1857-1858
[7]
Fig.7, p.8701-8702
[9]
Fig.7, p.24-25

References
[1]
Resource
Comments
Medline ID
PubMed ID 8860003
Journal Proteins
Year 1996
Volume 24
Pages 525-7
Authors Andersson A, Jordan D, Schneider G, Valent B, Lindqvist Y
Title Crystallization and preliminary x-ray diffraction study of 1 ,3,8-trihydroxynaphthalene reductase from Magnaporthe grisea.
Related PDB
Related UniProtKB
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS)
Medline ID 97094973
PubMed ID 8939741
Journal Structure
Year 1996
Volume 4
Pages 1161-70
Authors Andersson A, Jordan D, Schneider G, Lindqvist Y
Title Crystal structure of the ternary complex of 1,3,8-trihydroxynaphthalene reductase from Magnaporthe grisea with NADPH and an active-site inhibitor.
Related PDB 1ybv
Related UniProtKB Q12634
[3]
Resource
Comments
Medline ID
PubMed ID 9048570
Journal Biochemistry
Year 1997
Volume 36
Pages 1852-60
Authors Thompson JE, Basarab GS, Andersson A, Lindqvist Y, Jordan DB
Title Trihydroxynaphthalene reductase from Magnaporthe grisea: realization of an active center inhibitor and elucidation of the kinetic mechanism.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9001392
Journal FEBS Lett
Year 1997
Volume 400
Pages 173-6
Authors Andersson A, Jordan D, Schneider G, Lindqvist Y
Title A flexible lid controls access to the active site in 1,3,8-trihydroxynaphthalene reductase.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10743955
Journal Bioorg Med Chem Lett
Year 2000
Volume 10
Pages 491-4
Authors Liao DI, Basarab GS, Gatenby AA, Jordan DB
Title Selection of a potent inhibitor of trihydroxynaphthalene reductase by sorting disease control data.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10956664
Journal J Biol Chem
Year 2000
Volume 275
Pages 34867-72
Authors Thompson JE, Fahnestock S, Farrall L, Liao DI, Valent B, Jordan DB
Title The second naphthol reductase of fungal melanin biosynthesis in Magnaporthe grisea: tetrahydroxynaphthalene reductase.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 11467929
Journal Biochemistry
Year 2001
Volume 40
Pages 8696-704
Authors Liao DI, Thompson JE, Fahnestock S, Valent B, Jordan DB
Title A structural account of substrate and inhibitor specificity differences between two naphthol reductases.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 11552692
Journal J Mol Graph Model
Year 2001
Volume 19
Pages 434-47, 470-1
Authors Jordan DB, Basarab GS, Liao DI, Johnson WM, Winzenberg KN, Winkler DA
Title Structure-based design of inhibitors of the rice blast fungal enzyme trihydroxynaphthalene reductase.
Related PDB
Related UniProtKB
[9]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11342131
Journal Structure (Camb)
Year 2001
Volume 9
Pages 19-27
Authors Liao D, Basarab GS, Gatenby AA, Valent B, Jordan DB
Title Structures of trihydroxynaphthalene reductase-fungicide complexes: implications for structure-based design and catalysis.
Related PDB 1doh 1g0n 1g0o
Related UniProtKB

Comments
This enzyme was transferred from E.C. 1.3.1.50 to E.C. 1.1.1.252.
This enzyme belongs to the short-chain dehydrogenase/reductase (SDR) superfamily, along with Drosophia alcohol dehydrogenase (S00319 in EzCatDB). This enzyme has got a catalytic triad composed of conserved residues, Ser, Tyr, and Lys.
In addition to the catalytic triad, another tyrosine residue (Tyr223) is also involved in the active site in this enzyme.
According to the literature [9], this enzyme catalyzes isomerization followed by NADPH-dependent reduction, although the detailed reaction mechanism has not been elucidated so far. Thus, this enzyme seems to catalyze the following reactions:
(A) Isomerization of 1,3,6,8-Tetrahydroxynaphthalene, to form 3-keto intermediate (I00095):
(B) NADPH-dependent Reduction/Hydride transfer reaction:

Created Updated
2004-04-08 2011-07-04