PDBsum entry 3dbm

Lyase

PDB id: 3dbm

Contents

Protein chain

467 a.a.

Ligands

HEM

HO2

Waters ×147

References listed in PDB file

Key reference

Title

Modes of heme binding and substrate access for cytochrome p450 cyp74a revealed by crystal structures of allene oxide synthase.

Authors

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

Ref.

Proc Natl Acad Sci U S A, 2008, 105, 13883-13888. [DOI no: 10.1073/pnas.0804099105]

PubMed id

18787124

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.

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).