4UQF

CRYSTAL STRUCTURE OF LISTERIA MONOCYTOGENES GTP CYCLOHYDROLASE I

Summary for 4UQF

• Entry DOI: 10.2210/pdb4uqf/pdb
• Descriptor: GTP cyclohydrolase 1 (1 entity in total)
• Functional Keywords: hydrolase, folic acid biosynthesis, allosteric enzyme
• Biological source: Listeria monocytogenes
• Total number of polymer chains: 10
• Total formula weight: 229164.59

Authors

Schuessler, S.,Perbandt, M.,Fischer, M.,Graewert, T. (deposition date: 2014-06-23, release date: 2015-07-01, Last modification date: 2024-10-16)

Primary citation

Schussler, S.,Haase, I.,Perbandt, M.,Illarionov, B.,Siemens, A.,Richter, K.,Bacher, A.,Fischer, M.,Grawert, T.
Structure of GTP cyclohydrolase I from Listeria monocytogenes, a potential anti-infective drug target.
Acta Crystallogr.,Sect.F, 75:586-592, 2019

PubMed 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 = 53 µM; v = 180 nmol mg min). 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 = 0.226) by molecular replacement using human GTP cyclohydrolase I as a template. The protein is a D-symmetric decamer with ten topologically equivalent active sites. Screening a small library of about 9000 compounds afforded several inhibitors with IC 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.

PubMed: 31475925
DOI: 10.1107/S2053230X19010902

Experimental method

X-RAY DIFFRACTION (2.4 Å)