1hmp
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=5GP:GUANOSINE-5'-MONOPHOSPHATE'>5GP</scene> | |LIGAND= <scene name='pdbligand=5GP:GUANOSINE-5'-MONOPHOSPHATE'>5GP</scene> | ||
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1hmp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hmp OCA], [http://www.ebi.ac.uk/pdbsum/1hmp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1hmp RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The crystal structure of HGPRTase with bound GMP has been determined and refined to 2.5 A resolution. The enzyme has a core alpha/beta structure resembling the nucleotide-binding fold of dehydrogenases, and a second lobe composed of residues from the amino and carboxy termini. The GMP molecule binds in an anti conformation in a solvent-exposed cleft of the enzyme. Lys-165, which forms a hydrogen bond to O6 of GMP, appears to be critical for determining the specificity for guanine and hypoxanthine over adenine. The location of active site residues also provides evidence for a possible mechanism for general base-assisted HGPRTase catalysis. A rationalization of the effects on stability and activity of naturally occurring single amino acid mutations of HGPRTase is presented, including a discussion of several mutations at the active site that lead to Lesch-Nyhan syndrome. | The crystal structure of HGPRTase with bound GMP has been determined and refined to 2.5 A resolution. The enzyme has a core alpha/beta structure resembling the nucleotide-binding fold of dehydrogenases, and a second lobe composed of residues from the amino and carboxy termini. The GMP molecule binds in an anti conformation in a solvent-exposed cleft of the enzyme. Lys-165, which forms a hydrogen bond to O6 of GMP, appears to be critical for determining the specificity for guanine and hypoxanthine over adenine. The location of active site residues also provides evidence for a possible mechanism for general base-assisted HGPRTase catalysis. A rationalization of the effects on stability and activity of naturally occurring single amino acid mutations of HGPRTase is presented, including a discussion of several mutations at the active site that lead to Lesch-Nyhan syndrome. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: HPRT-related gout OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=308000 308000]], Lesch-Nyhan syndrome, 300322, OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=308000 308000]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Scapin, G.]] | [[Category: Scapin, G.]] | ||
[[Category: Xu, Y.]] | [[Category: Xu, Y.]] | ||
| - | [[Category: 5GP]] | ||
[[Category: transferase (glycosyltransferase)]] | [[Category: transferase (glycosyltransferase)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:07:42 2008'' |
Revision as of 18:07, 30 March 2008
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| , resolution 2.5Å | |||||||
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| Ligands: | |||||||
| Activity: | Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
THE CRYSTAL STRUCTURE OF HUMAN HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE WITH BOUND GMP
Overview
The crystal structure of HGPRTase with bound GMP has been determined and refined to 2.5 A resolution. The enzyme has a core alpha/beta structure resembling the nucleotide-binding fold of dehydrogenases, and a second lobe composed of residues from the amino and carboxy termini. The GMP molecule binds in an anti conformation in a solvent-exposed cleft of the enzyme. Lys-165, which forms a hydrogen bond to O6 of GMP, appears to be critical for determining the specificity for guanine and hypoxanthine over adenine. The location of active site residues also provides evidence for a possible mechanism for general base-assisted HGPRTase catalysis. A rationalization of the effects on stability and activity of naturally occurring single amino acid mutations of HGPRTase is presented, including a discussion of several mutations at the active site that lead to Lesch-Nyhan syndrome.
About this Structure
1HMP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystal structure of human hypoxanthine-guanine phosphoribosyltransferase with bound GMP., Eads JC, Scapin G, Xu Y, Grubmeyer C, Sacchettini JC, Cell. 1994 Jul 29;78(2):325-34. PMID:8044844
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