2BZ0

Crystal Structure of E. coli GTP cyclohydrolase II in complex with GTP analogue, GMPcPP, and Zinc

2BZ0 の概要

• エントリーDOI: 10.2210/pdb2bz0/pdb
• 関連するPDBエントリー: 2BZ1
• 分子名称: GTP CYCLOHYDROLASE II, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: riboflavin biosynthesis, gtp cyclohydrolase ii, catalytic zinc, gtp, hydrolase, magnesium
• 由来する生物種: ESCHERICHIA COLI
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44925.46

構造登録者

Ren, J.,Kotaka, M.,Lockyer, M.,Lamb, H.K.,Hawkins, A.R.,Stammers, D.K. (登録日: 2005-08-09, 公開日: 2005-08-19, 最終更新日: 2023-12-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.6 Å)