2i6b
From Proteopedia
(New page: 200px<br /> <applet load="2i6b" size="450" color="white" frame="true" align="right" spinBox="true" caption="2i6b, resolution 2.3Å" /> '''Human Adenosine Kina...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2i6b. | + | [[Image:2i6b.jpg|left|200px]]<br /><applet load="2i6b" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2i6b" size=" | + | |
caption="2i6b, resolution 2.3Å" /> | caption="2i6b, resolution 2.3Å" /> | ||
'''Human Adenosine Kinase in Complex with An Acetylinic Inhibitor'''<br /> | '''Human Adenosine Kinase in Complex with An Acetylinic Inhibitor'''<br /> | ||
| Line 8: | Line 7: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2I6B is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with 89I as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2I6B is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=89I:'>89I</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I6B OCA]. |
==Reference== | ==Reference== | ||
| Line 18: | Line 17: | ||
[[Category: protein-ligand complex]] | [[Category: protein-ligand complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:35:03 2008'' |
Revision as of 15:35, 15 February 2008
|
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 with as ligand. 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
Page seeded by OCA on Fri Feb 15 17:35:03 2008
