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 Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Lipoxygenases (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
- ↑ Koljak R, Boutaud O, Shieh BH, Samel N, Brash AR. Identification of a naturally occurring peroxidase-lipoxygenase fusion protein. Science. 1997 Sep 26;277(5334):1994-6. PMID:9302294
- ↑ Boutaud O, Brash AR. Purification and catalytic activities of the two domains of the allene oxide synthase-lipoxygenase fusion protein of the coral Plexaura homomalla. J Biol Chem. 1999 Nov 19;274(47):33764-70. PMID:10559269
- ↑ Oldham ML, Brash AR, Newcomer ME. 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. J Biol Chem. 2005 Nov 25;280(47):39545-52. Epub 2005 Sep 14. PMID:16162493 doi:10.1074/jbc.M506675200
