2i6a: Difference between revisions
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==Human Adenosine Kinase in Complex With 5'-Deoxy-5-Iodotubercidin== | ==Human Adenosine Kinase in Complex With 5'-Deoxy-5-Iodotubercidin== | ||
<StructureSection load='2i6a' size='340' side='right' caption='[[2i6a]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='2i6a' size='340' side='right' caption='[[2i6a]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2i6b|2i6b]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2i6b|2i6b]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2i6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i6a OCA], [http://pdbe.org/2i6a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i6a RCSB], [http://www.ebi.ac.uk/pdbsum/2i6a PDBsum]</span></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=2i6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i6a OCA], [http://pdbe.org/2i6a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i6a RCSB], [http://www.ebi.ac.uk/pdbsum/2i6a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2i6a ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2i6a ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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</div> | </div> | ||
<div class="pdbe-citations 2i6a" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 2i6a" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 11:24, 18 October 2017
Human Adenosine Kinase in Complex With 5'-Deoxy-5-IodotubercidinHuman Adenosine Kinase in Complex With 5'-Deoxy-5-Iodotubercidin
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAdenosine kinase (AK) is an enzyme responsible for converting endogenous adenosine (ADO) to adenosine monophosphate (AMP) in an adenosine triphosphate- (ATP-) dependent manner. The structure of AK consists of two domains, the first a large alpha/beta Rossmann-like nucleotide binding domain that forms the ATP binding site, and a smaller mixed alpha/beta domain, which, in combination with the larger domain, forms the ADO binding site and the site of phosphoryl transfer. AK inhibitors have been under investigation as antinociceptive, antiinflammatory, and anticonvulsant as well as antiinfective agents. In this work, we report the structures of AK in complex with two classes of inhibitors: the first, ADO-like, and the second, a novel alkynylpyrimidine series. The two classes of structures, which contain structurally similar substituents, reveal distinct binding modes in which the AK structure accommodates the inhibitor classes by a 30 degrees rotation of the small domain relative to the large domain. This change in binding mode stabilizes an open and a closed intermediate structural state and provide structural insight into the transition required for catalysis. This results in a significant rearrangement of both the protein active site and the orientation of the alkynylpyrimidine ligand when compared to the observed orientation of nucleosidic inhibitors or substrates. Crystal structures of human adenosine kinase inhibitor complexes reveal two distinct binding modes.,Muchmore SW, Smith RA, Stewart AO, Cowart MD, Gomtsyan A, Matulenko MA, Yu H, Severin JM, Bhagwat SS, Lee CH, Kowaluk EA, Jarvis MF, Jakob CL J Med Chem. 2006 Nov 16;49(23):6726-31. PMID:17154503[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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