2i5c
From Proteopedia
(New page: 200px<br /> <applet load="2i5c" size="450" color="white" frame="true" align="right" spinBox="true" caption="2i5c, resolution 1.75Å" /> '''Crystal structure o...) |
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caption="2i5c, resolution 1.75Å" /> | caption="2i5c, resolution 1.75Å" /> | ||
'''Crystal structure of the C-terminal PH domain of pleckstrin in complex with D-myo-Ins(1,2,3,4,5)P5'''<br /> | '''Crystal structure of the C-terminal PH domain of pleckstrin in complex with D-myo-Ins(1,2,3,4,5)P5'''<br /> | ||
| - | == | + | ==Overview== |
| - | + | BACKGROUND: Pleckstrin homology (PH) domains are one of the most prevalent, domains in the human proteome and represent the major, phosphoinositide-binding module. These domains are often found in, signaling proteins and function predominately by targeting their host, proteins to the cell membrane. Inositol phosphates, which are structurally, similar to phosphoinositides, are not only known to play a role as, signaling molecules but are also capable of being bound by PH domains., RESULTS: In the work presented here it is shown that the addition of, commercial myo-inositol hexakisphosphate (IP6) inhibited the binding of, the carboxy terminal PH domain of pleckstrin (C-PH) to, phosphatidylinositol 3,4-bisphosphate with an IC50 of 7.5 muM. In an, attempt to characterize this binding structurally, C-PH was crystallized, in the presence of IP6 and the structure was determined to 1.35 A., Examination of the resulting electron density unexpectedly revealed the, bound ligand to be D-myo-inositol 1,2,3,5,6-pentakisphosphate. CONCLUSION:, The discovery of D-myo-inositol 1,2,3,5,6-pentakisphosphate in the crystal, structure suggests that the inhibitory effects observed in the binding, studies may be due to this ligand rather than IP6. Analysis of the, protein-ligand interaction demonstrated that this myo-inositol, pentakisphosphate isomer interacts specifically with protein residues, known to be involved in phosphoinositide binding. In addition to this, a, structural alignment of other PH domains bound to inositol phosphates, containing either four or five phosphate groups revealed that the majority, of phosphate groups occupy conserved locations in the binding pockets of, PH domains. These findings, taken together with other recently reported, studies suggest that myo-inositol pentakisphosphates could act to regulate, PH domain-phosphoinositide interactions by directly competing for binding, thus playing an important role as signaling molecules. | |
==About this Structure== | ==About this Structure== | ||
| - | 2I5C 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 IP5 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2I5C 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=IP5:'>IP5</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I5C OCA]. |
| + | |||
| + | ==Reference== | ||
| + | Structural analysis of the carboxy terminal PH domain of pleckstrin bound to D-myo-inositol 1,2,3,5,6-pentakisphosphate., Jackson SG, Zhang Y, Haslam RJ, Junop MS, BMC Struct Biol. 2007 Nov 22;7:80. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18034889 18034889] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: protein-inositol phosphate complex]] | [[Category: protein-inositol phosphate complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 10:38:10 2008'' |
Revision as of 08:38, 23 January 2008
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Crystal structure of the C-terminal PH domain of pleckstrin in complex with D-myo-Ins(1,2,3,4,5)P5
Overview
BACKGROUND: Pleckstrin homology (PH) domains are one of the most prevalent, domains in the human proteome and represent the major, phosphoinositide-binding module. These domains are often found in, signaling proteins and function predominately by targeting their host, proteins to the cell membrane. Inositol phosphates, which are structurally, similar to phosphoinositides, are not only known to play a role as, signaling molecules but are also capable of being bound by PH domains., RESULTS: In the work presented here it is shown that the addition of, commercial myo-inositol hexakisphosphate (IP6) inhibited the binding of, the carboxy terminal PH domain of pleckstrin (C-PH) to, phosphatidylinositol 3,4-bisphosphate with an IC50 of 7.5 muM. In an, attempt to characterize this binding structurally, C-PH was crystallized, in the presence of IP6 and the structure was determined to 1.35 A., Examination of the resulting electron density unexpectedly revealed the, bound ligand to be D-myo-inositol 1,2,3,5,6-pentakisphosphate. CONCLUSION:, The discovery of D-myo-inositol 1,2,3,5,6-pentakisphosphate in the crystal, structure suggests that the inhibitory effects observed in the binding, studies may be due to this ligand rather than IP6. Analysis of the, protein-ligand interaction demonstrated that this myo-inositol, pentakisphosphate isomer interacts specifically with protein residues, known to be involved in phosphoinositide binding. In addition to this, a, structural alignment of other PH domains bound to inositol phosphates, containing either four or five phosphate groups revealed that the majority, of phosphate groups occupy conserved locations in the binding pockets of, PH domains. These findings, taken together with other recently reported, studies suggest that myo-inositol pentakisphosphates could act to regulate, PH domain-phosphoinositide interactions by directly competing for binding, thus playing an important role as signaling molecules.
About this Structure
2I5C is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Structural analysis of the carboxy terminal PH domain of pleckstrin bound to D-myo-inositol 1,2,3,5,6-pentakisphosphate., Jackson SG, Zhang Y, Haslam RJ, Junop MS, BMC Struct Biol. 2007 Nov 22;7:80. PMID:18034889
Page seeded by OCA on Wed Jan 23 10:38:10 2008
