3ZGN

Crystal structures of Escherichia coli IspH in complex with TMBPP a potent inhibitor of the methylerythritol phosphate pathway

Summary for 3ZGN

• Entry DOI: 10.2210/pdb3zgn/pdb
• Related: 3ZGL
• Descriptor: 4-HYDROXY-3-METHYLBUT-2-ENYL DIPHOSPHATE REDUCTASE, (2E)-3-methyl-4-sulfanylbut-2-en-1-yl trihydrogen diphosphate, IRON/SULFUR CLUSTER, ... (4 entities in total)
• Functional Keywords: oxidoreductase, mep pathway, inhibitors, 4fe-4s cluster
• Biological source: ESCHERICHIA COLI
• Total number of polymer chains: 2
• Total formula weight: 74538.63

Authors

Borel, F.,Barbier, E.,Kratsutsky, S.,Janthawornpong, K.,Rohmer, M.,Dale Poulter, C.,Ferrer, J.L.,Seemann, M. (deposition date: 2012-12-18, release date: 2013-01-09, Last modification date: 2023-12-20)

Primary citation

Borel, F.,Barbier, E.,Krasutsky, S.,Janthawornpong, K.,Chaignon, P.,Poulter, C.D.,Ferrer, J.L.,Seemann, M.
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.
Chembiochem, 18:2137-2144, 2017

PubMed Abstract: IspH, 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 Å 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.

PubMed: 28862365
DOI: 10.1002/cbic.201700363

Experimental method

X-RAY DIFFRACTION (1.95 Å)