PDBsum entry 1qxo

Lyase

PDB id: 1qxo

Contents

Protein chains

388 a.a. *

Ligands

NCO ×9

EDO ×7

FMN ×6

EPS ×4

Waters ×1929

* Residue conservation analysis

PDB id:

1qxo

Name:

Lyase

Title:

Crystal structure of chorismate synthase complexed with oxidized fmn and epsp

Structure:

Chorismate synthase. Chain: a, b, c, d. Synonym: 5-enolpyruvylshikimate-3-phosphate phospholyase. Engineered: yes

Source:

Streptococcus pneumoniae. Organism_taxid: 1313. Gene: aroc, sp1374 or spr1232. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.00Å R-factor: 0.160 R-free: 0.222

Authors:

J.Maclean,S.Ali

Key ref:

J.Maclean and S.Ali (2003). The structure of chorismate synthase reveals a novel flavin binding site fundamental to a unique chemical reaction. Structure, 11, 1499-1511. PubMed id: 14656434 DOI: 10.1016/j.str.2003.11.005

Date:

08-Sep-03 Release date: 23-Dec-03

Protein chains

P0A2Y6  (AROC_STRPN) -  Chorismate synthase from Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)

Seq: 388 a.a.

Struc: 388 a.a.

Enzyme reactions

• Enzyme class: E.C.4.2.3.5 - chorismate synthase.
• Pathway: Shikimate and Chorismate Biosynthesis
• Reaction: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate

5-O-(1-carboxyvinyl)-3-phosphoshikimate (Bound ligand (Het Group name = EPS) corresponds exactly) = chorismate + phosphate

• Cofactor: FMN

FMN (Bound ligand (Het Group name = FMN) corresponds exactly)

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

reference

DOI no: 10.1016/j.str.2003.11.005

Structure 11:1499-1511 (2003)

PubMed id: 14656434

The structure of chorismate synthase reveals a novel flavin binding site fundamental to a unique chemical reaction.

J.Maclean, S.Ali.

ABSTRACT

The crystal structure of chorismate synthase (CS) from Streptococcus pneumoniae has been solved to 2.0 A resolution in the presence of flavin mononucleotide (FMN) and the substrate 5-enolpyruvyl-3-shikimate phosphate (EPSP). CS catalyses the final step of the shikimate pathway and is a potential therapeutic target for the rational design of novel antibacterials, antifungals, antiprotozoals, and herbicides. CS is a tetramer with the monomer possessing a novel beta-alpha-beta fold. The interactions between the enzyme, cofactor, and substrate reveal the structural reasons underlying the unique catalytic mechanism and identify the amino acids involved. This structure provides the essential initial information necessary for the generation of novel anti-infective compounds by a structure-guided medicinal chemistry approach.

Selected figure(s)

Figure 3.
Figure 3. The Chorismate Synthase Active Site(A) Stereo representation of interactions made by FMN in the closed form. Active site residues are shown with green carbon atoms, FMN and EPSP with gray carbon atoms. Red spheres represent conserved water positions. Hydrogen bonds are shown as dashed lines. Some residues shown are from an adjacent monomer and form interactions that may stabilize the CS dimer. These residues are shown in darker green, and are labeled with green text, while residues from the monomer, which forms the majority of the active site, have black labels.(B) Stereo representation of interactions made by EPSP in the closed form. Active site residues are shown with green carbon atoms, FMN and EPSP with gray carbon atoms. Red spheres represent conserved water positions. Hydrogen bonds are shown as dashed lines.(C) Stereo diagram of the overlaid Ca traces of open (cyan ribbon) and closed (green ribbon) forms, showing differences in the conformations of loops L20 and L22. EPSP and FMN are shown with gray carbon atoms. The side chains of residues His 110, Tyr 317, Arg 337, Ser 338, and Asp 339 are shown for both forms (Open form: cyan carbons, closed form: green carbons). L22 shows the most significant movement, as demonstrated by the changes in the position of Arg 337 and Ser 338. Tyr 317 on loop L20 adopts different side chain conformations in open and closed forms, and may have a role in maintaining the closed conformation of loop L22. Hydrogen bond interactions between ligands and the highlighted residues in the closed form are shown as dashed lines. Corresponding interactions in the open form are omitted for clarity.

The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 1499-1511) copyright 2003.

Figure was selected by the author.