PDBsum entry 2glm

Lyase

PDB id: 2glm

Contents

Protein chains

(+ 0 more) 152 a.a. *

Ligands

BEN ×7

SCB

Metals

_CL ×6

Waters ×550

* Residue conservation analysis

PDB id:

2glm

Name:

Lyase

Title:

Crystal structure of (3r)-hydroxyacyl-acyl carrier protein dehydratase(fabz) from helicobacter pylori complexed with compound 2

Structure:

(3r)-hydroxymyristoyl-acyl carrier protein dehydratase. Chain: a, b, c, d, e, f. Synonym: fabz. Engineered: yes

Source:

Helicobacter pylori. Organism_taxid: 102617. Strain: ss1. Gene: fabz. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.60Å R-factor: 0.187 R-free: 0.241

Authors:

L.Zhang,W.Liu,X.Shen,H.Jiang

Key ref:

L.Zhang et al. (2008). Structural basis for catalytic and inhibitory mechanisms of beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ). J Biol Chem, 283, 5370-5379. PubMed id: 18093984 DOI: 10.1074/jbc.M705566200

Date:

05-Apr-06 Release date: 13-Mar-07

Protein chains

O25928  (FABZ_HELPY) -  3-hydroxyacyl-[acyl-carrier-protein] dehydratase FabZ from Helicobacter pylori (strain ATCC 700392 / 26695)

Seq: 159 a.a.

Struc: 152 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.4.2.1.59 - 3-hydroxyacyl-[acyl-carrier-protein] dehydratase.
• Reaction: a (3R)-hydroxyacyl-[ACP] = a (2E)-enoyl-[ACP] + H2O

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

Key reference

DOI no: 10.1074/jbc.M705566200

J Biol Chem 283:5370-5379 (2008)

PubMed id: 18093984

Structural basis for catalytic and inhibitory mechanisms of beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ).

L.Zhang, W.Liu, T.Hu, L.Du, C.Luo, K.Chen, X.Shen, H.Jiang.

ABSTRACT

beta-Hydroxyacyl-acyl carrier protein dehydratase (FabZ) is an important enzyme for the elongation cycles of both saturated and unsaturated fatty acids biosyntheses in the type II fatty acid biosynthesis system (FAS II) pathway. FabZ has been an essential target for the discovery of compounds effective against pathogenic microbes. In this work, to characterize the catalytic and inhibitory mechanisms of FabZ, the crystal structures of the FabZ of Helicobacter pylori (HpFabZ) and its complexes with two newly discovered inhibitors have been solved. Different from the structures of other bacterial FabZs, HpFabZ contains an extra short two-turn alpha-helix (alpha4) between alpha3 and beta3, which plays an important role in shaping the substrate-binding tunnel. Residue Tyr-100 at the entrance of the tunnel adopts either an open or closed conformation in the crystal structure. The crystal structural characterization, the binding affinity determination, and the enzymatic activity assay of the HpFabZ mutant (Y100A) confirm the importance of Tyr-100 in catalytic activity and substrate binding. Residue Phe-83 at the exit tunnel was also refined in two alternative conformations, leading the tunnel to form an L-shape and U-shape. All these data thus contributed much to understanding the catalytic mechanism of HpFabZ. In addition, the co-crystal structures of HpFabZ with its inhibitors have suggested that the enzymatic activity of HpFabZ could be inhibited either by occupying the entrance of the tunnel or plugging the tunnel to prevent the substrate from accessing the active site. Our study has provided some insights into the catalytic and inhibitory mechanisms of FabZ, thus facilitating antibacterial agent development.

Selected figure(s)

Figure 5.
FIGURE 5. Stereo view of the omit electron density map contoured at 1.0 around the compounds. Residues Tyr-100, Pro-112', and inhibitor are shown as sticks.

Figure 6.
FIGURE 6. Crystal structures of HpFabZ in complex with compounds 1 and 2. The dimers that bind to the compounds are represented. The hydrophobic surface of the active tunnel and the critical residues that interact with the compounds are also shown.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2008, 283, 5370-5379) copyright 2008.

Figures were selected by the author.