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Insights from the X-ray crystal structure of coral 8R-lipoxygenase: calcium activation via A C2-like domain and a structural basis of product chiralityInsights from the X-ray crystal structure of coral 8R-lipoxygenase: calcium activation via A C2-like domain and a structural basis of product chirality
Structural highlights
Function[AOSL_PLEHO] Bifunctional enzyme which is responsible for allene oxide biosynthesis via a two-step reaction which involves conversion of arachidonic acid to a 8R-hydroperoxide intermediate followed by conversion of the hydroperoxide to allene oxide.[1] [2] Evolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedLipoxygenases (LOXs) catalyze the regio- and stereospecific dioxygenation of polyunsaturated membrane-embedded fatty acids. We report here the 3.2 A resolution structure of 8R-LOX from the Caribbean sea whip coral Plexaura homomalla, a LOX isozyme with calcium dependence and the uncommon R chiral stereospecificity. Structural and spectroscopic analyses demonstrated calcium binding in a C2-like membrane-binding domain, illuminating the function of similar amino acids in calcium-activated mammalian 5-LOX, the key enzyme in the pathway to the pro-inflammatory leukotrienes. Mutation of Ca(2+)-ligating amino acids in 8R-LOX resulted not only in a diminished capacity to bind membranes, as monitored by fluorescence resonance energy transfer, but also in an associated loss of Ca(2+)-regulated enzyme activity. Moreover, a structural basis for R chiral specificity is also revealed; creation of a small oxygen pocket next to Gly(428) (Ala in all S-LOX isozymes) promoted C-8 oxygenation with R chirality on the activated fatty acid substrate. Insights from the X-ray crystal structure of coral 8R-lipoxygenase: calcium activation via a C2-like domain and a structural basis of product chirality.,Oldham ML, Brash AR, Newcomer ME J Biol Chem. 2005 Nov 25;280(47):39545-52. Epub 2005 Sep 14. PMID:16162493[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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