6enb | pdb_00006enb

LTA4 hydrolase (E297Q) mutant in complex with Pro-Gly-Pro peptide

spinqualitylabelsall models 6enb, resolution 1.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6enb is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.84Å Ligands: ACT, IMD, YB, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LKHA4_HUMAN Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity. Publication Abstract from PubMed Leukotriene A4 Hydrolase (LTA4H) is a bifunctional zinc metalloenzyme that comprises both epoxide hydrolase and aminopeptidase activity, exerted by two overlapping catalytic sites. The epoxide hydrolase function of the enzyme catalyzes the biosynthesis of the pro-inflammatory lipid mediator leukotriene (LT) B4. Recent literature suggests that the aminopeptidase function of LTA4H is responsible for degradation of the tripeptide Pro-Gly-Pro (PGP) for which neutrophil chemotactic activity has been postulated. It has been speculated that the design of epoxide hydrolase selective LTA4H inhibitors that spare the aminopeptidase pocket may therefore lead to more efficacious anti-inflammatory drugs. In this study, we conducted a high throughput screen (HTS) for LTA4H inhibitors and attempted to rationally design compounds that would spare the PGP degrading function. While we were able to identify compounds with preference for the epoxide hydrolase function, absolute selectivity was not achievable for highly potent compounds. In order to assess the relevance of designing such aminopeptidase-sparing LTA4H inhibitors, we studied the role of PGP in inducing inflammation in different settings in wild type and LTA4H deficient (LTA4H KO) animals but could not confirm its chemotactic potential. Attempting to design highly potent epoxide hydrolase selective LTA4H inhibitors, therefore seems to be neither feasible nor relevant. Feasibility and physiological relevance of designing highly potent aminopeptidase-sparing leukotriene A4 hydrolase inhibitors.,Numao S, Hasler F, Laguerre C, Srinivas H, Wack N, Jager P, Schmid A, Osmont A, Rothlisberger P, Houguenade J, Bergsdorf C, Dawson J, Carte N, Hofmann A, Markert C, Hardaker L, Billich A, Wolf RM, Penno CA, Bollbuck B, Miltz W, Rohn TA Sci Rep. 2017 Oct 19;7(1):13591. doi: 10.1038/s41598-017-13490-1. PMID:29051536 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Leukotriene A4 Hydrolase

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