4NRE: The Structure of Human 15-lipoxygenase-2 With a Substrate Mimic

Citation:
Abstract
Atherosclerosis is associated with chronic inflammation occurring over decades. The enzyme 15-lipoxygenase-2 (15-LOX-2) is highly expressed in large atherosclerotic plaques, and its activity has been linked to the progression of macrophages to the lipid-laden foam cells present in atherosclerotic plaques. We report here the crystal structure of human 15-LOX-2 in complex with an inhibitor that appears to bind as a substrate mimic. 15-LOX-2 contains a long loop, composed of hydrophobic amino acids, which projects from the amino-terminal membrane-binding domain. The loop is flanked by two Ca(2+)-binding sites that confer Ca(2+)-dependent membrane binding. A comparison of the human 15-LOX-2 and 5-LOX structures reveals similarities at the active sites, as well striking differences that can be exploited for design of isoform-selective inhibitors.
PDB ID: 4NREDownload
MMDB ID: 117533
PDB Deposition Date: 2013/11/26
Updated in MMDB: 2014/10
Experimental Method:
x-ray diffraction
Resolution: 2.63  Å
Source Organism:
Similar Structures:
Biological Unit for 4NRE: monomeric; determined by author
Molecular Components in 4NRE
Label Count Molecule
Protein (1 molecule)
1
Arachidonate 15-lipoxygenase B(Gene symbol: ALOX15B)
Molecule annotation
Chemicals (20 molecules)
1
1
2
2
3
12
4
2
5
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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