Structural highlights
4qwt is a 4 chain structure with sequence from Plexaura homomalla. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | X-ray diffraction, Resolution 2.002Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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]
Publication Abstract from PubMed
Lipoxygenases (LOX) play critical roles in mammalian biology in the generation of potent lipid mediators of the inflammatory response; consequently they are targets for the development of isoform-specific inhibitors. The regio- and stereo-specificity of the oxygenation of polyunsaturated fatty acids by the enzymes is understood in terms of the chemistry, but structural observation of the enzyme-substrate interactions is lacking. Although several LOX crystal structures are available, heretofore the rapid oxygenation of bound substrate has precluded capture of the enzyme-substrate complex, leaving a gap between chemical and structural insights. In this report we describe the 2.0 A resolution structure of 8R-LOX in complex with arachidonic acid (AA) obtained under anaerobic conditions. Subtle rearrangements, primarily in the side chains of three amino acids, allow binding of AA in a catalytically competent conformation. Accompanying experimental work supports a model in which both substrate tethering and cavity depth contribute to positioning the appropriate carbon at the catalytic machinery.
Crystal Structure of a Lipoxygenase in Complex with Substrate: the Arachidonic Acid Binding Site of 8R-Lipoxygenase.,Neau DB, Bender G, Boeglin WE, Bartlett SG, Brash AR, Newcomer ME J Biol Chem. 2014 Sep 17. pii: jbc.M114.599662. PMID:25231982[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
- ↑ Neau DB, Bender G, Boeglin WE, Bartlett SG, Brash AR, Newcomer ME. Crystal Structure of a Lipoxygenase in Complex with Substrate: the Arachidonic Acid Binding Site of 8R-Lipoxygenase. J Biol Chem. 2014 Sep 17. pii: jbc.M114.599662. PMID:25231982 doi:http://dx.doi.org/10.1074/jbc.M114.599662
