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STRUCTURE OF LEUKOTRIENE A4 HYDROLASE COMPLEXED WITH BESTATIN.STRUCTURE OF LEUKOTRIENE A4 HYDROLASE COMPLEXED WITH BESTATIN.
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedLeukotriene (LT) A(4) hydrolase/aminopeptidase (LTA4H) is a bifunctional zinc enzyme that catalyzes the biosynthesis of LTB4, a potent lipid chemoattractant involved in inflammation, immune responses, host defense against infection, and PAF-induced shock. The high resolution crystal structure of LTA4H in complex with the competitive inhibitor bestatin reveals a protein folded into three domains that together create a deep cleft harboring the catalytic Zn(2+) site. A bent and narrow pocket, shaped to accommodate the substrate LTA(4), constitutes a highly confined binding region that can be targeted in the design of specific anti-inflammatory agents. Moreover, the structure of the catalytic domain is very similar to that of thermolysin and provides detailed insight into mechanisms of catalysis, in particular the chemical strategy for the unique epoxide hydrolase reaction that generates LTB(4). Crystal structure of human leukotriene A(4) hydrolase, a bifunctional enzyme in inflammation.,Thunnissen MM, Nordlund P, Haeggstrom JZ Nat Struct Biol. 2001 Feb;8(2):131-5. PMID:11175901[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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