Structural highlights
Function[Q9HXM5_PSEAE] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth (By similarity).[HAMAP-Rule:MF_01964] Publication Abstract from PubMedInosine-5'-monophosphate dehydrogenase (IMPDH) is an essential enzyme in many bacterial pathogens and is considered as a potential drug target for the development of new antibacterial agents. Our recent work has revealed the crucial role of one of the two structural domains (i.e. Bateman domain) in the regulation of the quaternary structure and enzymatic activity of bacterial IMPDHs. Thus, we have screened chemical libraries to search for compounds targeting the Bateman domain and identified first in-class allosteric inhibitors of a bacterial IMPDH. These inhibitors were shown to counteract the activation by the natural positive effector, MgATP, and to block the enzyme in its apo conformation (low affinity for IMP). Our structural studies demonstrate the versatility of the Bateman domain to accommodate totally unrelated chemical scaffolds and pave the way for the development of allosteric inhibitors, an avenue little explored until now. First-in-class allosteric inhibitors of bacterial IMPDHs.,Alexandre T, Lupan A, Helynck O, Vichier-Guerre S, Dugue L, Gelin M, Haouz A, Labesse G, Munier-Lehmann H Eur J Med Chem. 2019 Feb 2;167:124-132. doi: 10.1016/j.ejmech.2019.01.064. PMID:30769241[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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This page was last modified 15:20, 27 February 2019.