3zgn | pdb_00003zgn
Crystal structures of Escherichia coli IspH in complex with TMBPP a potent inhibitor of the methylerythritol phosphate pathway
Structural highlights
FunctionISPH_ECOLI Converts 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate into isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Is also involved in penicillin tolerance and control of the stringent response. Seems to directly or indirectly interact with RelA to maintain it in an inactive form during normal growth.[1] [2] [3] Publication Abstract from PubMedIspH, also called LytB, a protein involved in the biosynthesis of isoprenoids through the methylerythritol phosphate pathway, is an attractive target for the development of new antimicrobial drugs. Here, we report crystal structures of Escherichia coli IspH in complex with the two most potent inhibitors: (E)-4-mercapto-3-methylbut-2-en-1-yl diphosphate (TMBPP) and (E)-4-amino-3-methylbut-2-en-1-yl diphosphate (AMBPP) at 1.95 and 1.7 A resolution, respectively. The structure of the E. coli IspH:TMBPP complex exhibited two conformers of the inhibitor. This unexpected feature was exploited to design and evolve new antimicrobial candidates in silico. Further Insight into Crystal Structures of Escherichia coli IspH/LytB in Complex with Two Potent Inhibitors of the MEP Pathway: A Starting Point for Rational Design of New Antimicrobials.,Borel F, Barbier E, Krasutsky S, Janthawornpong K, Chaignon P, Poulter CD, Ferrer JL, Seemann M Chembiochem. 2017 Nov 2;18(21):2137-2144. doi: 10.1002/cbic.201700363. Epub 2017 , Oct 2. PMID:28862365[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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