PDBsum entry 4h6c

Isomerase

PDB id: 4h6c

Contents

Protein chains

(+ 6 more) 180 a.a.

Ligands

PO4 ×17

HEZ ×6

Waters ×2594

PDB id:

4h6c

Name:

Isomerase

Title:

Crystal structure of the allene oxide cyclase 1 from physcomitrella patens

Structure:

Allene oxide cyclase. Chain: a, d, c, b, e, f, g, h, i, j, k, l. Engineered: yes

Source:

Physcomitrella patens. Organism_taxid: 3218. Gene: aoc, aoc1. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.35Å R-factor: 0.140 R-free: 0.174

Authors:

P.Neumann,R.Ficner

Key ref:

P.Neumann et al. (2012). Crystal structures of Physcomitrella patens AOC1 and AOC2: insights into the enzyme mechanism and differences in substrate specificity. Plant Physiol, 160, 1251-1266. PubMed id: 22987885

Date:

19-Sep-12 Release date: 17-Oct-12

Protein chains

Q8GS38  (Q8GS38_PHYPA) -  allene-oxide cyclase from Physcomitrium patens

Seq: 189 a.a.

Struc: 180 a.a.

Enzyme reactions

• Enzyme class: E.C.5.3.99.6 - allene-oxide cyclase.
• Reaction: (9Z,13S,15Z)-12,13-epoxyoctadeca-9,11,15-trienoate = (9S,13S,15Z)-12- oxophyto-10,15-dienoate

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

Key reference

Plant Physiol 160:1251-1266 (2012)

PubMed id: 22987885

Crystal structures of Physcomitrella patens AOC1 and AOC2: insights into the enzyme mechanism and differences in substrate specificity.

P.Neumann, F.Brodhun, K.Sauer, C.Herrfurth, M.Hamberg, J.Brinkmann, J.Scholz, A.Dickmanns, I.Feussner, R.Ficner.

ABSTRACT

In plants, oxylipins regulate developmental processes and defense responses. The first specific step in the biosynthesis of the cyclopentanone class of oxylipins is catalyzed by allene oxide cyclase (AOC) that forms cis(+)-12-oxo-phytodienoic acid. The moss Physcomitrella patens has two AOCs (PpAOC1 and PpAOC2) with different substrate specificities for C(18)- and C(20)-derived substrates, respectively. To better understand AOC's catalytic mechanism and to elucidate the structural properties that explain the differences in substrate specificity, we solved and analyzed the crystal structures of 36 monomers of both apo and ligand complexes of PpAOC1 and PpAOC2. From these data, we propose the following intermediates in AOC catalysis: (1) a resting state of the apo enzyme with a closed conformation, (2) a first shallow binding mode, followed by (3) a tight binding of the substrate accompanied by conformational changes in the binding pocket, and (4) initiation of the catalytic cycle by opening of the epoxide ring. As expected, the substrate dihydro analog cis-12,13S-epoxy-9Z,15Z-octadecadienoic acid did not cyclize in the presence of PpAOC1; however, when bound to the enzyme, it underwent isomerization into the corresponding trans-epoxide. By comparing complex structures of the C(18) substrate analog with in silico modeling of the C(20) substrate analog bound to the enzyme allowed us to identify three major molecular determinants responsible for the different substrate specificities (i.e. larger active site diameter, an elongated cavity of PpAOC2, and two nonidentical residues at the entrance of the active site).