2bz0 | pdb_00002bz0
CRYSTAL STRUCTURE OF E. COLI GTP CYCLOHYDROLASE II IN COMPLEX WITH GTP ANALOGUE, GMPCPP, AND ZINC
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Overview
GTP cyclohydrolase II converts GTP to, 2,5-diamino-6-beta-ribosyl-4(3H)-pyrimidinone 5'-phosphate, formate and, pyrophosphate, the first step in riboflavin biosynthesis. The essential, role of riboflavin in metabolism and the absence of GTP cyclohydrolase II, in higher eukaryotes makes it a potential novel selective antimicrobial, drug target. GTP cyclohydrolase II catalyzes a distinctive overall, reaction from GTP cyclohydrolase I; the latter converts GTP to, dihydroneopterin triphosphate, utilized in folate and tetrahydrobiopterin, biosynthesis. The structure of GTP cyclohydrolase II determined at 1.54-A, resolution reveals both a different protein fold to GTP cyclohydrolase I, and distinctive molecular recognition determinants for GTP; although in, both enzymes there is a bound catalytic zinc. The GTP cyclohydrolase, II.GMPCPP complex structure shows Arg(128) interacting with the, alpha-phosphonate, and thus in the case of GTP, Arg(128) is positioned to, act as the nucleophile for pyrophosphate release and formation of the, proposed covalent guanylyl-GTP cyclohydrolase II intermediate. Tyr(105) is, identified as playing a key role in GTP ring opening; it is, hydrogen-bonded to the zinc-activated water molecule, the latter being, positioned for nucleophilic attack on the guanine C-8 atom. Although GTP, cyclohydrolase I and GTP cyclohydrolase II both use a zinc ion for the GTP, ring opening and formate release, different residues are utilized in each, case to catalyze this reaction step.
About this Structure
2BZ0 is a Single protein structure of sequence from Escherichia coli with ZN, MG and G2P as ligands. Active as GTP cyclohydrolase II, with EC number 3.5.4.25 Known structural/functional Site: AC1. Full crystallographic information is available from OCA.
Reference
GTP cyclohydrolase II structure and mechanism., Ren J, Kotaka M, Lockyer M, Lamb HK, Hawkins AR, Stammers DK, J Biol Chem. 2005 Nov 4;280(44):36912-9. Epub 2005 Aug 22. PMID:16115872
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