4QWT
Anaerobic crystal structure of delta413-417:GS LOX in complex with arachidonate
Summary for 4QWT
| Entry DOI | 10.2210/pdb4qwt/pdb |
| Related | 2FNQ 3FG3 3FG4 3FGI |
| Descriptor | Allene oxide synthase-lipoxygenase protein, FE (II) ION, CALCIUM ION, ... (8 entities in total) |
| Functional Keywords | iron binding, membrane-associated, oxidoreductase |
| Biological source | Plexaura homomalla (black sea rod) |
| Cellular location | Cytoplasm : O16025 |
| Total number of polymer chains | 4 |
| Total formula weight | 321738.85 |
| Authors | Neau, D.B.,Newcomer, M.E. (deposition date: 2014-07-17, release date: 2014-09-24, Last modification date: 2023-09-20) |
| Primary citation | Neau, D.B.,Bender, G.,Boeglin, W.E.,Bartlett, S.G.,Brash, A.R.,Newcomer, M.E. Crystal Structure of a Lipoxygenase in Complex with Substrate: THE ARACHIDONIC ACID-BINDING SITE OF 8R-LIPOXYGENASE. J.Biol.Chem., 289:31905-31913, 2014 Cited by PubMed Abstract: 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 Å resolution structure of 8R-LOX in complex with arachidonic acid obtained under anaerobic conditions. Subtle rearrangements, primarily in the side chains of three amino acids, allow binding of arachidonic acid 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. PubMed: 25231982DOI: 10.1074/jbc.M114.599662 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.002 Å) |
Structure validation
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