PDBsum entry 4std

Lyase

PDB id: 4std

Contents

Protein chains

164 a.a. *

Ligands

BFS ×3

Waters ×135

* Residue conservation analysis

PDB id:

4std

Name:

Lyase

Title:

High resolution structures of scytalone dehydratase-inhibitor complexes crystallized at physiological ph

Structure:

Scytalone dehydratase. Chain: a, b, c. Synonym: sdh. Engineered: yes

Source:

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

Biol. unit:

Hexamer (from PQS)

Resolution:

2.15Å R-factor: 0.224 R-free: 0.278

Authors:

Z.Wawrzak,T.Sandalova,J.J.Steffens,G.S.Basarab,T.Lundqvist, Y.Lindqvist,D.B.Jordan

Key ref:

Z.Wawrzak et al. (1999). High-resolution structures of scytalone dehydratase-inhibitor complexes crystallized at physiological pH. Proteins, 35, 425-439. PubMed id: 10382670 DOI: 10.1002/(SICI)1097-0134(19990601)35:4<425::AID-PROT6>3.3.CO;2-T

Date:

10-Feb-99 Release date: 29-Dec-99

Protein chains

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

Seq: 172 a.a.

Struc: 164 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.4.2.1.94 - scytalone dehydratase.
• Reaction: scytalone = 1,3,8-trihydroxynaphthalene + H2O

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

Added reference

DOI no: 10.1002/(SICI)1097-0134(19990601)35:4<425::AID-PROT6>3.3.CO;2-T

Proteins 35:425-439 (1999)

PubMed id: 10382670

High-resolution structures of scytalone dehydratase-inhibitor complexes crystallized at physiological pH.

Z.Wawrzak, T.Sandalova, J.J.Steffens, G.S.Basarab, T.Lundqvist, Y.Lindqvist, D.B.Jordan.

ABSTRACT

Scytalone dehydratase is a molecular target of inhibitor design efforts aimed at preventing the fungal disease caused by Magnaporthe grisea. A method for cocrystallization of enzyme with inhibitors at neutral pH has produced several crystal structures of enzyme-inhibitor complexes at resolutions ranging from 1.5 to 2.2 A. Four high resolution structures of different enzyme-inhibitor complexes are described. In contrast to the original X-ray structure of the enzyme, the four new structures have well-defined electron density for the loop region comprising residues 115-119 and a different conformation between residues 154 and 160. The structure of the enzyme complex with an aminoquinazoline inhibitor showed that the inhibitor is in a position to form a hydrogen bond with the amide of the Asn131 side chain and with two water molecules in a fashion similar to the salicylamide inhibitor in the original structure, thus confirming design principles. The aminoquinazoline structure also allows for a more confident assignment of donors and acceptors in the hydrogen bonding network. The structures of the enzyme complexes with two dichlorocyclopropane carboxamide inhibitors showed the two chlorine atoms nearly in plane with the amide side chain of Asn131. The positions of Phe53 and Phe158 are significantly altered in the new structures in comparison to the two structures obtained from crystals grown at acidic pH. The multiple structures help define the mobility of active site amino acids critical for catalysis and inhibitor binding.

Selected figure(s)

Figure 1.
Figure 1. The fungal melanin biosynthetic pathway. 4HNR, tetrahydroxynapthalene reductase; SD, scytalone dehydratase; 3HNR, trihydroxynapthalene reductase.

Figure 3.
Figure 3. Stereo views of the electron densities (2F[O] - F[C]) surrounding the inhibitors and the two water molecules in the active site of scytalone dehydratase. (A) Inhibitor 1. (B) Inhibitor 2. (C) Inhibitor 3. (D) Inhibitor 4.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (1999, 35, 425-439) copyright 1999.

Figures were selected by an automated process.