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Publication Abstract from PubMed

A putative open reading frame encoding GTP cyclohydrolase I from Listeria monocytogenes was expressed in a recombinant Escherichia coli strain. The recombinant protein was purified and was confirmed to convert GTP to dihydroneopterin triphosphate (Km = 53 microM; vmax = 180 nmol mg(-1) min(-1)). The protein was crystallized from 1.3 M sodium citrate pH 7.3 and the crystal structure was solved at a resolution of 2.4 A (Rfree = 0.226) by molecular replacement using human GTP cyclohydrolase I as a template. The protein is a D5-symmetric decamer with ten topologically equivalent active sites. Screening a small library of about 9000 compounds afforded several inhibitors with IC50 values in the low-micromolar range. Several inhibitors had significant selectivity with regard to human GTP cyclohydrolase I. Hence, GTP cyclohydrolase I may be a potential target for novel drugs directed at microbial infections, including listeriosis, a rare disease with high mortality.

Structure of GTP cyclohydrolase I from Listeria monocytogenes, a potential anti-infective drug target.,Schussler S, Haase I, Perbandt M, Illarionov B, Siemens A, Richter K, Bacher A, Fischer M, Grawert T Acta Crystallogr F Struct Biol Commun. 2019 Sep 1;75(Pt 9):586-592. doi:, 10.1107/S2053230X19010902. Epub 2019 Aug 30. PMID:31475925^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.