1rzy

<StructureSection load='1rzy' size='340' side='right' caption='[[1rzy]], [[Resolution|resolution]] 1.80&Aring;' scene=''>

<table><tr><td colspan='2'>[[1rzy]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RZY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1RZY FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5AS:5-O-(N-ETHYL-SULFAMOYL)ADENOSINE'>5AS</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6rhn|6rhn]], [[5rhn|5rhn]]</td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HINT1, HINT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rzy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rzy OCA], [http://pdbe.org/1rzy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1rzy RCSB], [http://www.ebi.ac.uk/pdbsum/1rzy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1rzy ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/HINT1_RABIT HINT1_RABIT]] Hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2.

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

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.

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<ref>PMID:14982931</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

</div>

<div class="pdbe-citations 1rzy" style="background-color:#fffaf0;"></div>

*[[Histidine triad nucleotide-binding protein|Histidine triad nucleotide-binding protein]]

[[Category: European rabbit]]

[[Category: Adams, M]]

[[Category: Baraniak, J]]

[[Category: Blackburn, G M]]

[[Category: Brenner, C]]

[[Category: Kaczmarek, R]]

[[Category: Krakowiak, A K]]

[[Category: Mekhalfia, A]]

[[Category: Pace, H C]]

[[Category: Stec, W J]]

[[Category: Protein-inhibitor complex]]