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==Human Histidine Triad Nucleotide Binding Protein 2 (hHint2) triciribine 5'-monoposphate catalytic product complex==
<StructureSection load='5km5' size='340' side='right'caption='[[5km5]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5km5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KM5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KM5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TR5:5-METHYL-1-(5-O-PHOSPHONO-BETA-D-RIBOFURANOSYL)-1,5-DIHYDRO-1,4,5,6,8-PENTAAZAACENAPHTHYLEN-3-AMINE'>TR5</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5km5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5km5 OCA], [https://pdbe.org/5km5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5km5 RCSB], [https://www.ebi.ac.uk/pdbsum/5km5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5km5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HINT2_HUMAN HINT2_HUMAN] Hydrolase probably involved in steroid biosynthesis. May play a role in apoptosis. Has adenosine phosphoramidase activity.<ref>PMID:16762638</ref> <ref>PMID:18653718</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Nucleotide analogs that incorporate a metabolically labile nucleoside phosphoramidate (a ProTide) have found utility as prodrugs. In humans, ProTides can be cleaved by human histidine triad nucleotide binding protein 1 (hHint1) to expose the nucleotide monophosphate. Activation by this route circumvents highly selective nucleoside kinases that limit the use of nucleosides as prodrugs. To better understand the diversity of potential substrates of hHint1, we created and studied a series of phosphoramidate nucleosides. Using a combination of enzyme kinetics, X-ray crystallography, and isothermal titration calorimetry with both wild-type and inactive mutant enzymes, we have been able to explore the energetics of substrate binding and establish a structural basis for catalytic efficiency. Diverse nucleobases are well tolerated, but portions of the ribose are needed to position substrates for catalysis. Beneficial characteristics of the amine leaving group are also revealed. Structural principles revealed by these results may be exploited to tune the rate of substrate hydrolysis to strategically alter the intracellular release of the product nucleoside monophosphate from the ProTide.

A Crystal Structure-Based Guide to the Design of Human Histidine Triad Nucleotide Binding Protein 1 (hHint1) Activated ProTides.,Maize KM, Shah R, Strom A, Kumarapperuma SC, Zhou AL, Wagner CR, Finzel BC Mol Pharm. 2017 Oct 2. doi: 10.1021/acs.molpharmaceut.7b00664. PMID:28968488<ref>PMID:28968488</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5km5" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histidine triad nucleotide-binding protein 3D structures|Histidine triad nucleotide-binding protein 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Finzel BC]]
[[Category: Maize KM]]