1wuq
From Proteopedia
(New page: 200px<br /><applet load="1wuq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wuq, resolution 2.0Å" /> '''Structure of GTP cycl...) |
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| - | [[Image:1wuq.gif|left|200px]]<br /><applet load="1wuq" size=" | + | [[Image:1wuq.gif|left|200px]]<br /><applet load="1wuq" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1wuq, resolution 2.0Å" /> | caption="1wuq, resolution 2.0Å" /> | ||
'''Structure of GTP cyclohydrolase I Complexed with 8-oxo-GTP'''<br /> | '''Structure of GTP cyclohydrolase I Complexed with 8-oxo-GTP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | GTP cyclohydrolase I (GTPCH1) catalyzes the conversion of GTP to | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1WUQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with ZN and 8GT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/GTP_cyclohydrolase_I GTP cyclohydrolase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.16 3.5.4.16] Full crystallographic information is available from [http:// | + | 1WUQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=8GT:'>8GT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/GTP_cyclohydrolase_I GTP cyclohydrolase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.16 3.5.4.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WUQ OCA]. |
==Reference== | ==Reference== | ||
| - | 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., Tanaka Y, Nakagawa N, Kuramitsu S, Yokoyama S, Masui R, J Biochem | + | 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., Tanaka Y, Nakagawa N, Kuramitsu S, Yokoyama S, Masui R, J Biochem. 2005 Sep;138(3):263-75. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16169877 16169877] |
[[Category: GTP cyclohydrolase I]] | [[Category: GTP cyclohydrolase I]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Masui, R.]] | [[Category: Masui, R.]] | ||
[[Category: Nakagawa, N.]] | [[Category: Nakagawa, N.]] | ||
| - | [[Category: RSGI, RIKEN | + | [[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]] |
[[Category: Tanaka, Y.]] | [[Category: Tanaka, Y.]] | ||
[[Category: Yokoyama, S.]] | [[Category: Yokoyama, S.]] | ||
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[[Category: tetrahydrobiopterin]] | [[Category: tetrahydrobiopterin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:48:20 2008'' |
Revision as of 13:48, 21 February 2008
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Structure of GTP cyclohydrolase I Complexed with 8-oxo-GTP
Overview
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.
About this Structure
1WUQ is a Single protein structure of sequence from Thermus thermophilus with and as ligands. Active as GTP cyclohydrolase I, with EC number 3.5.4.16 Full crystallographic information is available from OCA.
Reference
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., Tanaka Y, Nakagawa N, Kuramitsu S, Yokoyama S, Masui R, J Biochem. 2005 Sep;138(3):263-75. PMID:16169877
Page seeded by OCA on Thu Feb 21 15:48:20 2008
Categories: GTP cyclohydrolase I | Single protein | Thermus thermophilus | Kuramitsu, S. | Masui, R. | Nakagawa, N. | RSGI, RIKEN Structural Genomics/Proteomics Initiative. | Tanaka, Y. | Yokoyama, S. | 8GT | ZN | Beta barrel | Hydrolase | National project on protein structural and functional analyses | Nppsfa | Protein-inhibitor complex | Pteridine | Riken structural genomics/proteomics initiative | Rsgi | Structural genomics | Tetrahydrobiopterin
