PDBsum entry 2std

Lyase

PDB id

2std

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Contents

			Protein chain

					162 a.a. *

			Ligands

					SO4


					CRP

			Waters ×174

* Residue conservation analysis

PDB id:

2std

Links

Name:

Lyase

Title:

Scytalone dehydratase complexed with tight-binding inhibitor carpropamid

Structure:

Scytalone dehydratase. Chain: a. Engineered: yes

Source:

Magnaporthe grisea. Organism_taxid: 148305. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Trimer (from PQS)

Resolution:

2.10Å

R-factor:

0.179

R-free:

0.259

Authors:

M.Nakasako,T.Motoyama,Y.Kurahashi,I.Yamaguchi

Key ref:

M.Nakasako et al. (1998). 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. Biochemistry, 37, 9931-9939. PubMed id: 9665698 DOI: 10.1021/bi980321b

Date:

21-Dec-97

Release date:

16-Feb-99

PROCHECK

	Headers

	References

Protein chain

P56221 (SCYD_MAGO7) - Scytalone dehydratase from Pyricularia oryzae (strain 70-15 / ATCC MYA-4617 / FGSC 8958)

Seq: Struc:					172 a.a. 162 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.4.2.1.94 - scytalone dehydratase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

scytalone = 1,3,8-trihydroxynaphthalene + H2O

scytalone	=	1,3,8-trihydroxynaphthalene	+	H2O

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1021/bi980321b	Biochemistry 37:9931-9939 (1998)
PubMed id: 9665698

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.
M.Nakasako, T.Motoyama, Y.Kurahashi, I.Yamaguchi.

ABSTRACT

Scytalone dehydratase is a member of the group of enzymes involved in fungal melanin biosynthesis in a phytopathogenic fungus, Pyricularia oryzae, which causes rice blast disease. Carpropamid [(1RS,3SR)-2, 2-dichloro-N-[(R)-1-(4-chlorophenyl)ethyl]-1-ethyl-3-methylcyclopropa necarboxamide] is a tight-binding inhibitor of the enzyme. To clarify the structural basis for tight-binding inhibition, the crystal structure of the enzyme complexed with carpropamid was analyzed using diffraction data collected at 100 K. The structural model was refined to a crystallographic R-factor of 0.180 against reflections up to a resolution of 2.1 A. Carpropamid was bound in a hydrophobic cavity of the enzyme. Three types of interactions appeared to contribute to the binding. (i) A hydrogen bond was formed between a chloride atom in the dichloromethylethylcyclopropane ring of carpropamid and Asn-131 of the enzyme. (ii) The (chlorophenyl)ethyl group of carpropamid built strong contacts with Val-75, and this group further formed a cluster of aromatic rings together with four aromatic residues in the enzyme (Tyr-50, Phe-53, Phe-158, and Phe-162). (iii) Two hydration water molecules bound to the carboxamide group of carpropamid, and they were further hydrogen-bonded to Tyr-30, Tyr-50, His-85, and His-110. As a result of interactions between carpropamid and the phenylalanine residues (Phe-158 and Phe-162) in the C-terminal region of the enzyme, the C-terminal region completely covered the inhibitor, ensuring its localization in the cavity.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21040590

V.Bhadauria, L.X.Wang, and Y.L.Peng (2010).
Proteomic changes associated with deletion of the Magnaporthe oryzae conidial morphology-regulating gene COM1.

Biol Direct, 5, 61.

17202683

D.S.Kim, Y.M.Jeong, I.K.Park, H.G.Hahn, H.K.Lee, S.B.Kwon, J.H.Jeong, S.J.Yang, U.D.Sohn, and K.C.Park (2007).
A new 2-imino-1,3-thiazoline derivative, KHG22394, inhibits melanin synthesis in mouse B16 melanoma cells.

Biol Pharm Bull, 30, 180-183.

15306376

M.Nakasako (2004).
Water-protein interactions from high-resolution protein crystallography.

Philos Trans R Soc Lond B Biol Sci, 359, 1191.

15056895

N.Yamada, T.Motoyama, M.Nakasako, S.Kagabu, T.Kudo, and I.Yamaguchi (2004).
Enzymatic characterization of scytalone dehydratase Val75Met variant found in melanin biosynthesis dehydratase inhibitor (MBI-D) resistant strains of the rice blast fungus.

Biosci Biotechnol Biochem, 68, 615-621.

10636235

D.B.Jordan, and G.S.Basarab (2000).
Binding dynamics of two water molecules constrained within the scytalone dehydratase binding pocket.

Bioorg Med Chem Lett, 10, 23-26.

10097077

A.E.Nixon, S.M.Firestine, F.G.Salinas, and S.J.Benkovic (1999).
Rational design of a scytalone dehydratase-like enzyme using a structurally homologous protein scaffold.

Proc Natl Acad Sci U S A, 96, 3568-3571.

10386946

G.S.Basarab, D.B.Jordan, T.C.Gehret, R.S.Schwartz, and Z.Wawrzak (1999).
Design of scytalone dehydratase inhibitors as rice blast fungicides: derivatives of norephedrine.

Bioorg Med Chem Lett, 9, 1613-1618.

10382670

Z.Wawrzak, T.Sandalova, J.J.Steffens, G.S.Basarab, T.Lundqvist, Y.Lindqvist, and D.B.Jordan (1999).
High-resolution structures of scytalone dehydratase-inhibitor complexes crystallized at physiological pH.

Proteins, 35, 425-439.

PDB codes:

4std 5std 6std 7std

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.