PDBsum entry 3d04

Lyase

PDB id: 3d04

Contents

Protein chains

(+ 0 more) 152 a.a. *

Ligands

BEN ×6

SAK ×2

Metals

_CL ×6

Waters ×439

* Residue conservation analysis

PDB id:

3d04

Name:

Lyase

Title:

Crystal structure of (3r)-hydroxyacyl-acyl carrier protein dehydratase (fabz) from helicobacter pylori in complex with sakuranetin

Structure:

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

Source:

Helicobacter pylori. Organism_taxid: 210. Strain: ss1. Gene: fabz. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.40Å R-factor: 0.191 R-free: 0.212

Authors:

L.Zhang,Y.Kong,D.Wu,X.Shen,H.Jiang

Key ref:

L.Zhang et al. (2008). Three flavonoids targeting the beta-hydroxyacyl-acyl carrier protein dehydratase from Helicobacter pylori: crystal structure characterization with enzymatic inhibition assay. Protein Sci, 17, 1971-1978. PubMed id: 18780820 DOI: 10.1110/ps.036186.108

Date:

01-May-08 Release date: 09-Dec-08

Protein chains

Q5G940  (Q5G940_HELPX) -  3-hydroxyacyl-[acyl-carrier-protein] dehydratase FabZ from Helicobacter pylori

Seq: 159 a.a.

Struc: 152 a.a.

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: 10.1110/ps.036186.108

Protein Sci 17:1971-1978 (2008)

PubMed id: 18780820

Three flavonoids targeting the beta-hydroxyacyl-acyl carrier protein dehydratase from Helicobacter pylori: crystal structure characterization with enzymatic inhibition assay.

L.Zhang, Y.Kong, D.Wu, H.Zhang, J.Wu, J.Chen, J.Ding, L.Hu, H.Jiang, X.Shen.

ABSTRACT

Flavonoids are the major functional components of many herbal and insect preparations and demonstrate varied pharmacological functions including antibacterial activity. Here by enzymatic assay and crystal structure analysis, we studied the inhibition of three flavonoids (quercetin, apigenin, and (S)-sakuranetin) against the beta-hydroxyacyl-acyl carrier protein dehydratase from Helicobacter pylori (HpFabZ). These three flavonoids are all competitive inhibitors against HpFabZ by either binding to the entrance of substrate tunnel B (binding model A) or plugging into the tunnel C near the catalytic residues (binding model B) mainly by hydrophobic interaction and hydrogen-bond pattern. Surrounded by hydrophobic residues of HpFabZ at both positions of models A and B, the methoxy group at C-7 of (S)-sakuranetin seems to play an important role for the inhibitor's binding to HpFabZ, partly responsible for the higher inhibitory activity of (S)-sakuranetin than those of quercetin and apigenin against HpFabZ (IC(50) in microM: (S)-sakuranetin, 2.0 +/- 0.1; quercetin: 39.3 +/- 2.7; apigenin, 11.0 +/- 2.5). Our work is expected to supply useful information for understanding the potential antibacterial mechanism of flavonoids.

Selected figure(s)

Figure 2.
Stereoview of the omit electron density maps contoured at 1.0 [sigma] around quercetin (A,B), apigenin (C,D), and (S)-sakuranetin (E,F). Quercetin, apigenin, and (S)-sakuranetin are shown as sticks and colored in wheat, yellow, and olive, respectively. Monomers A, B, C, and D are colored in green, cyan, magenta, and orange, respectively. The pictures were generated using the program PyMOL (DeLano Scientific).

Figure 3.
The interaction between HpFabZ and inhibitors. (A,B) Binding positions of quercetin (salmon), apigenin (yellow), and (S)-sakuranetin (purple-blue) around the tunnel entrance (model A) or near the catalytic residues (model B) are shown. In model A, the inhibitors bind to the entrance of tunnel B linearly through hydrophobic interactions and are stacked between residues Tyr100 and Pro112[prime prime or minute]. In model B, inhibitors embed into tunnel C near the catalytic residues and are located in the hydrophobic pocket. The electrostatic surface of the active tunnel is rendered by a color ramp from red to blue. (C --H) Quercetin colored in wheat (C,D), apigenin colored in yellow (E,F), and (S)-sakuranetin colored in olive (G,H) interact with surrounding residues and water molecules in HpFabZ. Hydrogen bonds are shown as black dashes. Residues are labeled and colored in green, cyan, magenta, and orange for monomers A, B, C, and D, respectively.

The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (2008, 17, 1971-1978) copyright 2008.

Figures were selected by an automated process.