1rzy
From Proteopedia
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|PDB= 1rzy |SIZE=350|CAPTION= <scene name='initialview01'>1rzy</scene>, resolution 1.80Å | |PDB= 1rzy |SIZE=350|CAPTION= <scene name='initialview01'>1rzy</scene>, resolution 1.80Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=5AS:5 | + | |LIGAND= <scene name='pdbligand=5AS:5'-O-(N-ETHYL-SULFAMOYL)ADENOSINE'>5AS</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= HINT1, HINT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 Oryctolagus cuniculus]) | |GENE= HINT1, HINT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 Oryctolagus cuniculus]) | ||
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[[Category: hit protein; protein-inhibitor complex]] | [[Category: hit protein; protein-inhibitor complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 13:32:53 2008'' |
Revision as of 11:32, 23 March 2008
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| , resolution 1.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | HINT1, HINT (Oryctolagus cuniculus) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of rabbit Hint complexed with N-ethylsulfamoyladenosine
Overview
Hint, histidine triad nucleotide-binding protein, is a universally conserved enzyme that hydrolyzes AMP linked to lysine and, in yeast, functions as a positive regulator of the RNA polymerase II C-terminal domain kinase, Kin28. To explore the biochemical and structural bases for the adenosine phosphoramidate hydrolase activity of rabbit Hint, we synthesized novel substrates linking a p-nitroaniline group to adenylate (AMP-pNA) and inhibitors that consist of an adenosine group and 5'-sulfamoyl (AdoOSO(2)NH(2)) or N-ethylsulfamoyl (AdoOSO(2)NHCH(2)CH(3)) group. AMP-pNA is a suitable substrate for Hint that allowed characterization of the inhibitors; titration of each inhibitor into AMP-pNA assays revealed their K(i) values. The N-ethylsulfamoyl derivative has a 13-fold binding advantage over the sulfamoyl adenosine. The 1.8-A cocrystal structure of rabbit Hint with N-ethylsulfamoyl adenosine revealed a binding site for the ethyl group against Trp-123, a residue that reaches across the Hint dimer interface to interact with the alkyl portion of the inhibitor and, presumably, the alkyl portion of a lysyl substrate. Ser-107 is positioned to donate a hydrogen bond to the leaving group nitrogen. Consistent with a role in acid-base catalysis, the Hint S107A mutant protein displayed depressed catalytic activity.
About this Structure
1RZY is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.
Reference
Biochemical, crystallographic, and mutagenic characterization of hint, the AMP-lysine hydrolase, with novel substrates and inhibitors., Krakowiak A, Pace HC, Blackburn GM, Adams M, Mekhalfia A, Kaczmarek R, Baraniak J, Stec WJ, Brenner C, J Biol Chem. 2004 Apr 30;279(18):18711-6. Epub 2004 Feb 24. PMID:14982931
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