1WUR

Structure of GTP cyclohydrolase I Complexed with 8-oxo-dGTP

Summary for 1WUR

• Entry DOI: 10.2210/pdb1wur/pdb
• Related: 1WUQ
• Descriptor: GTP cyclohydrolase I, ZINC ION, 8-OXO-2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: beta barrel, protein-inhibitor complex, hydrolase, pteridine, tetrahydrobiopterin, structural genomics, nppsfa, national project on protein structural and functional analyses, riken structural genomics/proteomics initiative, rsgi
• Biological source: Thermus thermophilus
• Total number of polymer chains: 5
• Total formula weight: 125799.60

Authors

Tanaka, Y.,Nakagawa, N.,Masui, R.,Yokoyama, S.,Kuramitsu, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2004-12-08, release date: 2005-07-19, Last modification date: 2024-03-13)

Primary citation

Tanaka, Y.,Nakagawa, N.,Kuramitsu, S.,Yokoyama, S.,Masui, R.
Novel reaction mechanism of GTP cyclohydrolase I. High-resolution X-ray crystallography of Thermus thermophilus HB8 enzyme complexed with a transition state analogue, the 8-oxoguanine derivative
J.Biochem.(Tokyo), 138:263-275, 2005

PubMed Abstract: GTP cyclohydrolase I (GTPCH1) catalyzes the conversion of GTP to dihydroneopterin 3'-triphosphate. We found that an 8-oxoguanine derivative of GTP (8-oxo-GTP) strongly bound to GTPCH1 from Thermus thermophilus HB8 (tGTPCH1) as a competitive inhibitor. The affinity of 8-oxo-GTP was three orders of magnitude greater than that of GTP. These results suggest that 8-oxo-GTP is a transition state analogue of GTPCH1. We have solved the X-ray crystal structures of tGTPCH1 complexed with 8-oxo-GTP and 8-oxo-dGTP at 2.0 and 1.8 A resolution, respectively, as well as the free form of the enzyme at 2.2 A resolution. In the structure of tGTPCH1 complexed with 8-oxo-GTP or 8-oxo-dGTP, the oxygen atoms at O8 of the 8-oxoguanine groups, together with residues Cys108, His111 and Cys179, are coordinated to the zinc ion. The water molecule between Ndelta1 of His177 and N7 of 8-oxoguanine is conserved in both structures. These structural data are in accordance with one of the proposed transition states. Superimpositioning of the structures indicates the imidazole ring of His110 is rotated, implying concomitant proton transfer to the ribose ring O4'. Based on these structural data we propose a novel reaction mechanism for GTPCH1.

PubMed: 16169877
DOI: 10.1093/jb/mvi120

Experimental method

X-RAY DIFFRACTION (1.82 Å)