Structure of GTP cyclohydrolase I from Listeria monocytogenes, a potential anti-infective drug target.

ABSTRACT: 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 (K_m = 53 µM; v_max = 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 Å (R_free = 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 inh

SUBMITTER: Schussler S 

PROVIDER: S-EPMC6718149 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature