2i6b
From Proteopedia
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| - | [[Image:2i6b.jpg|left|200px]] | + | [[Image:2i6b.jpg|left|200px]] |
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| - | '''Human Adenosine Kinase in Complex with An Acetylinic Inhibitor''' | + | {{Structure |
| + | |PDB= 2i6b |SIZE=350|CAPTION= <scene name='initialview01'>2i6b</scene>, resolution 2.3Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=89I:5-[4-(DIMETHYLAMINO)PHENYL]-6-[(6-MORPHOLIN-4-YLPYRIDIN-3-YL)ETHYNYL]PYRIMIDIN-4-AMINE'>89I</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= ADK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Human Adenosine Kinase in Complex with An Acetylinic Inhibitor''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2I6B is a [ | + | 2I6B is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I6B OCA]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17154503 17154503] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: protein-ligand complex]] | [[Category: protein-ligand complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:25:59 2008'' |
Revision as of 15:26, 20 March 2008
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| , resolution 2.3Å | |||||||
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| Ligands: | |||||||
| Gene: | ADK (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human Adenosine Kinase in Complex with An Acetylinic Inhibitor
Overview
Adenosine 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.
About this Structure
2I6B is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
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