2bz1
From Proteopedia
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==Overview== | ==Overview== | ||
| - | GTP cyclohydrolase II converts GTP to | + | 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== | ==About this Structure== | ||
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[[Category: GTP cyclohydrolase II]] | [[Category: GTP cyclohydrolase II]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Hawkins, A | + | [[Category: Hawkins, A R.]] |
[[Category: Kotaka, M.]] | [[Category: Kotaka, M.]] | ||
| - | [[Category: Lamb, H | + | [[Category: Lamb, H K.]] |
[[Category: Lockyer, M.]] | [[Category: Lockyer, M.]] | ||
[[Category: Ren, J.]] | [[Category: Ren, J.]] | ||
| - | [[Category: Stammers, D | + | [[Category: Stammers, D K.]] |
[[Category: GOL]] | [[Category: GOL]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
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[[Category: riboflavin biosynthesis]] | [[Category: riboflavin biosynthesis]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:43:07 2008'' |
Revision as of 14:43, 21 February 2008
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CRYSTAL STRUCTURE OF APO E. COLI GTP CYCLOHYDROLASE II
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
2BZ1 is a Single protein structure of sequence from Escherichia coli with , , and as ligands. Active as GTP cyclohydrolase II, with EC number 3.5.4.25 Known structural/functional Site: . 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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