1b07: Difference between revisions
New page: left|200px<br /><applet load="1b07" size="450" color="white" frame="true" align="right" spinBox="true" caption="1b07, resolution 2.50Å" /> '''CRK SH3 DOMAIN COMPL... |
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[[Image:1b07.gif|left|200px]]<br /><applet load="1b07" size=" | [[Image:1b07.gif|left|200px]]<br /><applet load="1b07" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1b07, resolution 2.50Å" /> | caption="1b07, resolution 2.50Å" /> | ||
'''CRK SH3 DOMAIN COMPLEXED WITH PEPTOID INHIBITOR'''<br /> | '''CRK SH3 DOMAIN COMPLEXED WITH PEPTOID INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
Src homology 3 (SH3) and WW protein interaction domains bind specific | Src homology 3 (SH3) and WW protein interaction domains bind specific proline-rich sequences. However, instead of recognizing critical prolines on the basis of side chain shape or rigidity, these domains broadly accepted amide N-substituted residues. Proline is apparently specifically selected in vivo, despite low complementarity, because it is the only endogenous N-substituted amino acid. This discriminatory mechanism explains how these domains achieve specific but low-affinity recognition, a property that is necessary for transient signaling interactions. The mechanism can be exploited: screening a series of ligands in which key prolines were replaced by nonnatural N-substituted residues yielded a ligand that selectively bound the Grb2 SH3 domain with 100 times greater affinity. | ||
==About this Structure== | ==About this Structure== | ||
1B07 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with PYL as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1B07 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=PYL:'>PYL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B07 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Cohen, F | [[Category: Cohen, F E.]] | ||
[[Category: Lim, W | [[Category: Lim, W A.]] | ||
[[Category: Nguyen, J | [[Category: Nguyen, J T.]] | ||
[[Category: Turck, C | [[Category: Turck, C W.]] | ||
[[Category: Zuckermann, R | [[Category: Zuckermann, R N.]] | ||
[[Category: PYL]] | [[Category: PYL]] | ||
[[Category: inhibitors]] | [[Category: inhibitors]] | ||
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[[Category: signal transduction]] | [[Category: signal transduction]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:50:08 2008'' | ||
Revision as of 09:50, 21 February 2008
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CRK SH3 DOMAIN COMPLEXED WITH PEPTOID INHIBITOR
Overview
Src homology 3 (SH3) and WW protein interaction domains bind specific proline-rich sequences. However, instead of recognizing critical prolines on the basis of side chain shape or rigidity, these domains broadly accepted amide N-substituted residues. Proline is apparently specifically selected in vivo, despite low complementarity, because it is the only endogenous N-substituted amino acid. This discriminatory mechanism explains how these domains achieve specific but low-affinity recognition, a property that is necessary for transient signaling interactions. The mechanism can be exploited: screening a series of ligands in which key prolines were replaced by nonnatural N-substituted residues yielded a ligand that selectively bound the Grb2 SH3 domain with 100 times greater affinity.
About this Structure
1B07 is a Single protein structure of sequence from Mus musculus with PYL as ligand. Full crystallographic information is available from OCA.
Reference
Exploiting the basis of proline recognition by SH3 and WW domains: design of N-substituted inhibitors., Nguyen JT, Turck CW, Cohen FE, Zuckermann RN, Lim WA, Science. 1998 Dec 11;282(5396):2088-92. PMID:9851931
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