2P0M: Revised Structure Of Rabbit Reticulocyte 15s-Lipoxygenase

Citation:
Abstract
Lipoxygenases (LOXs) are a family of nonheme iron dioxygenases that catalyze the regioselective and stereospecific hydroperoxidation of polyunsaturated fatty acids, and are involved in a variety of inflammatory diseases and cancers. The crystal structure of rabbit 15S-LOX1 that was reported by Gillmor et al. in 1997 has played key roles for understanding the properties of mammalian LOXs. In this structure, three segments, including 12 residues in the superficial alpha2 helix, are absent and have usually been described as "disordered." By reinterpreting the original crystallographic data we were able to elucidate two different conformations of the molecule, both having well ordered alpha2 helices. Surprisingly, one molecule contained an inhibitor and the other did not, thereby adopting a closed and an open form, respectively. They differed in the conformation of the segments that were absent in the original structure, which is highlighted by a 12 A movement of alpha2. Consequently, they showed a difference in the size and shape of the substrate-binding cavity. The new model should provide new insight into the catalytic mechanism involving induced conformational change of the binding pocket. It may also be helpful for the structure-based design of LOX inhibitors.
PDB ID: 2P0MDownload
MMDB ID: 59213
PDB Deposition Date: 2007/2/28
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 2P0M: monomeric; determined by author and by software (PQS)
Molecular Components in 2P0M
Label Count Molecule
Protein (1 molecule)
1
Arachidonate 15-lipoxygenase(Gene symbol: ALOX15)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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