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''' | ||
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[[Category: Muchmore, S W.]] | [[Category: Muchmore, S W.]] | ||
[[Category: 5'-deoxy-5-iodotubercidin]] | [[Category: 5'-deoxy-5-iodotubercidin]] | ||
[[Category: | [[Category: Protein-ligand complex]] | ||
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Revision as of 07:07, 4 May 2008
Human Adenosine Kinase in Complex With 5'-Deoxy-5-Iodotubercidin
OverviewOverview
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 StructureAbout this Structure
2I6A is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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 Page seeded by OCA on Sun May 4 07:07:35 2008