PDBsum entry 3dbm

Lyase

PDB id: 3dbm

Contents

Protein chain

467 a.a. *

Ligands

HEM

HO2

Waters ×147

* Residue conservation analysis

PDB id:

3dbm

Name:

Lyase

Title:

Crystal structure of allene oxide synthase

Structure:

Cytochrome p450 74a2. Chain: a. Synonym: allene oxide synthase, rubber particle protein, rpp. Engineered: yes

Source:

Parthenium argentatum. Guayule rubber plant. Organism_taxid: 35935. Gene: cyp74a2, rpp30. Expressed in: escherichia coli.

Resolution:

2.60Å R-factor: 0.219 R-free: 0.270

Authors:

L.Li,X.Wang

Key ref:

L.Li et al. (2008). Modes of heme binding and substrate access for cytochrome P450 CYP74A revealed by crystal structures of allene oxide synthase. Proc Natl Acad Sci U S A, 105, 13883-13888. PubMed id: 18787124 DOI: 10.1073/pnas.0804099105

Date:

01-Jun-08 Release date: 23-Sep-08

Protein chain

Q40778  (C74A2_PARAR) -  Allene oxide synthase from Parthenium argentatum

Seq: 473 a.a.

Struc: 467 a.a.

Enzyme reactions

• Enzyme class: E.C.4.2.1.92 - hydroperoxide dehydratase.
• Reaction: (13S)-hydroperoxy-(9Z,11E,15Z)-octadecatrienoate = (9Z,13S,15Z)-12,13- epoxyoctadeca-9,11,15-trienoate + H2O
• Cofactor: Heme-thiolate

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

Key reference

DOI no: 10.1073/pnas.0804099105

Proc Natl Acad Sci U S A 105:13883-13888 (2008)

PubMed id: 18787124

Modes of heme binding and substrate access for cytochrome P450 CYP74A revealed by crystal structures of allene oxide synthase.

L.Li, Z.Chang, Z.Pan, Z.Q.Fu, X.Wang.

ABSTRACT

Cytochrome P450s exist ubiquitously in all organisms and are involved in many biological processes. Allene oxide synthase (AOS) is a P450 enzyme that plays a key role in the biosynthesis of oxylipin jasmonates, which are involved in signal and defense reactions in higher plants. The crystal structures of guayule (Parthenium argentatum) AOS (CYP74A2) and its complex with the substrate analog 13(S)-hydroxyoctadeca-9Z,11E-dienoic acid have been determined. The structures exhibit a classic P450 fold but possess a heme-binding mode with an unusually long heme binding loop and a unique I-helix. The structures also reveal two channels through which substrate and product may access and leave the active site. The entrances are defined by a loop between beta3-2 and beta3-3. Asn-276 in the substrate binding site may interact with the substrate's hydroperoxy group and play an important role in catalysis, and Lys-282 at the entrance may control substrate access and binding. These studies provide both structural insights into AOS and related P450s and a structural basis to understand the distinct reaction mechanism.

Selected figure(s)

Figure 2.
Ribbon diagram of the structure of AOS with bound heme and 13(S)-HODE. The α- and β-domains are shown in cyan and magenta with the secondary structures and the N and C termini labeled. The heme and 13(S)-HODE molecules are shown as ball-and-stick models. Figs. 2, 3, 4A, and 5 were prepared with MOLSCRIPT (45) and RASTER3D (46).

Figure 3.
Heme-binding site. (A) Stereo diagram shows heme molecule and its interactions with AOS. The structure of heme is shown as a ball-and-stick model. (B) Stereo diagram shows a comparison of I-helix of AOS (in cyan) and human P450 2C9 (in gray). (C) Stereo diagram shows a comparison of heme-binding loop of AOS (in cyan) and human P450 2C9 (in gray).

Figures were selected by an automated process.