2BZ1

CRYSTAL STRUCTURE OF APO E. COLI GTP CYCLOHYDROLASE II

Summary for 2BZ1

• Entry DOI: 10.2210/pdb2bz1/pdb
• Related: 2BZ0
• Descriptor: GTP CYCLOHYDROLASE II, ZINC ION, SULFATE ION, ... (6 entities in total)
• Functional Keywords: riboflavin biosynthesis, gtp cyclohydrolase ii, catalytic zinc, hydrolase, magnesium
• Biological source: ESCHERICHIA COLI
• Total number of polymer chains: 1
• Total formula weight: 22622.38

Authors

Ren, J.,Kotaka, M.,Lockyer, M.,Lamb, H.K.,Hawkins, A.R.,Stammers, D.K. (deposition date: 2005-08-09, release date: 2005-08-19, Last modification date: 2024-11-06)

Primary citation

Ren, J.,Kotaka, M.,Lockyer, M.,Lamb, H.K.,Hawkins, A.R.,Stammers, D.K.
GTP Cyclohydrolase II Structure and Mechanism.
J.Biol.Chem., 280:36912-, 2005

PubMed Abstract: 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.

PubMed: 16115872
DOI: 10.1074/JBC.M507725200

Experimental method

X-RAY DIFFRACTION (1.54 Å)