2P0M

Revised structure of rabbit reticulocyte 15S-lipoxygenase

Summary for 2P0M

• Entry DOI: 10.2210/pdb2p0m/pdb
• Descriptor: Arachidonate 15-lipoxygenase, FE (II) ION, (2E)-3-(2-OCT-1-YN-1-YLPHENYL)ACRYLIC ACID, ... (4 entities in total)
• Functional Keywords: rabbit, 15s-lipoxygenase, twin, pseudo symmetry, conformational change, arachidonate, iron, oxidoreductase
• Biological source: Oryctolagus cuniculus (rabbit)
• Cellular location: Cytoplasm: P12530
• Total number of polymer chains: 2
• Total formula weight: 150891.28

Authors

Choi, J.,Chon, J.K.,Kim, S.,Shin, W. (deposition date: 2007-02-28, release date: 2007-10-09, Last modification date: 2024-03-13)

Primary citation

Choi, J.,Chon, J.K.,Kim, S.,Shin, W.
Conformational flexibility in mammalian 15S-lipoxygenase: Reinterpretation of the crystallographic data.
Proteins, 70:1023-1032, 2008

PubMed 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.

PubMed: 17847087
DOI: 10.1002/prot.21590

Experimental method

X-RAY DIFFRACTION (2.4 Å)