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3CHR

Crystal structure of leukotriene A4 hydrolase in complex with 4-amino-N-[4-(phenylmethoxy)phenyl]-butanamide

Summary for 3CHR
Entry DOI10.2210/pdb3chr/pdb
Related1GW6 1H19 1HS6 1SQM 2VJ8 3CHO 3CHP 3CHQ 3CHS
DescriptorLeukotriene A-4 hydrolase, ZINC ION, YTTERBIUM (III) ION, ... (6 entities in total)
Functional Keywordsepoxide hydrolase, alpha-beta protein, leukotriene biosynthesis, metalloprotease, inhibitor complex, alternative splicing, cytoplasm, metal-binding, multifunctional enzyme, zinc, hydrolase
Biological sourceHomo sapiens (human)
Total number of polymer chains1
Total formula weight69824.66
Authors
Thunnissen, M.M.G.M.,Adler, M.,Whitlow, M. (deposition date: 2008-03-10, release date: 2008-04-22, Last modification date: 2024-02-21)
Primary citationKirkland, T.A.,Adler, M.,Bauman, J.G.,Chen, M.,Haeggstrom, J.Z.,King, B.,Kochanny, M.J.,Liang, A.M.,Mendoza, L.,Phillips, G.B.,Thunnissen, M.,Trinh, L.,Whitlow, M.,Ye, B.,Ye, H.,Parkinson, J.,Guilford, W.J.
Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A4 hydrolase.
Bioorg.Med.Chem., 16:4963-4983, 2008
Cited by
PubMed Abstract: Leukotriene B(4) (LTB(4)) is a potent pro-inflammatory mediator that has been implicated in the pathogenesis of multiple diseases, including psoriasis, inflammatory bowel disease, multiple sclerosis and asthma. As a method to decrease the level of LTB(4) and possibly identify novel treatments, inhibitors of the LTB(4) biosynthetic enzyme, leukotriene A(4) hydrolase (LTA(4)-h), have been explored. Here we describe the discovery of a potent inhibitor of LTA(4)-h, arylamide of glutamic acid 4f, starting from the corresponding glycinamide 2. Analogs of 4f are then described, focusing on compounds that are both active and stable in whole blood. This effort culminated in the identification of amino alcohol 12a and amino ester 6b which meet these criteria.
PubMed: 18394906
DOI: 10.1016/j.bmc.2008.03.042
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.2 Å)
Structure validation

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