4h6c
Crystal Structure of the Allene Oxide Cyclase 1 from Physcomitrella patens
Structural highlights
FunctionPublication Abstract from PubMedIn plants oxylipins regulate developmental processes and defence 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 + 2) with different substrate specificities for C18 and C20-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 2. From these data we propose the following intermediates in AOC catalysis: (i) a resting state of the apo enzyme with a closed conformation, (ii) a first shallow binding mode, followed by (iii) a tight binding of the substrate accompanied by conformational changes in the binding pocket, and (iv) initiation of the catalytic cycle by opening of the epoxide ring. As expected, the substrate dihydro analogue cis-12,13-epoxyoctadecadienoic 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 C18 substrate analogue with in silico modeling of the C20 substrate analogue bound to the enzyme allowed us to identify three major molecular determinants responsible for the different substrate specificities, i.e. larger active site diameter and an elongated cavity of PpAOC2 and two non-identical residues at the entrance of the active site. Crystal structures of Physcomitrella patens AOC1 and 2: Insights into the enzyme mechanism and differences in substrate specificity.,Neumann P, Brodhun F, Sauer K, Herrfurth C, Hamberg M, Brinkmann J, Scholz J, Dickmanns A, Feussner I, Ficner R Plant Physiol. 2012 Sep 17. PMID:22987885[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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