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| - | [[Image:1a1c.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1a1c| PDB=1a1c | SCENE= }} | | {{STRUCTURE_1a1c| PDB=1a1c | SCENE= }} |
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| - | '''C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-PHOSPHOTYR-GLU-(N-ME(-(CH2)3-CYCLOPENTYL))'''
| + | ===C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-PHOSPHOTYR-GLU-(N-ME(-(CH2)3-CYCLOPENTYL))=== |
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| - | ==Overview==
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| - | Thermodynamic measurements, structural determinations, and molecular computations were applied to a series of peptide ligands of the pp60(c-src) SH2 domain in an attempt to understand the critical binding determinants for this class of molecules. Isothermal titration calorimetry (ITC) measurements were combined with structural data derived from X-ray crystallographic studies on 12 peptide-SH2 domain complexes. The peptide ligands studied fall into two general classes: (1) dipeptides of the general framework N-acetylphosphotyrosine (or phosphotyrosine replacement)-Glu or methionine (or S-methylcysteine)-X, where X represents a hydrophobic amine, and (2) tetra- or pentapeptides of the general framework N-acetylphosphotyrosine-Glu-Glu-Ile-X, where X represents either Glu, Gln, or NH2. Dipeptide analogs which featured X as either hexanolamine or heptanolamine were able to pick up new hydrogen bonds involving their hydroxyl groups within a predominantly lipophilic surface cavity. However, due to internal strain as well as the solvent accessibility of the new hydrogen bonds formed, no net increase in binding affinity was observed. Phosphatase-resistant benzylmalonate and alpha,alpha-difluorobenzyl phosphonate analogs of phosphotyrosine retained some binding affinity for the pp60(c-src) SH2 domain but caused local structural perturbations in the phosphotyrosine-binding site. In the case where a reversible covalent thiohemiacetal was formed between a formylated phosphotyrosine analog and the thiol side chain of Cys-188, deltaS was 25.6 cal/(mol K) lower than for the nonformylated phosphotyrosine parent. Normal mode calculations show that the dramatic decrease in entropy observed for the covalent thiohemiacetal complex is due to the inability of the phosphotyrosine moiety to transform lost rotational and translational degrees of freedom into new vibrational modes.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_9174343}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9174343 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_9174343}} |
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| | ==Disease== | | ==Disease== |
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| | [[Category: Jordan, S.]] | | [[Category: Jordan, S.]] |
| | [[Category: Shewchuk, L.]] | | [[Category: Shewchuk, L.]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 09:39:44 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 15:46:44 2008'' |
Revision as of 12:46, 30 June 2008
Template:STRUCTURE 1a1c
C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-PHOSPHOTYR-GLU-(N-ME(-(CH2)3-CYCLOPENTYL))
Template:ABSTRACT PUBMED 9174343
Disease
Known disease associated with this structure: Colon cancer, advanced OMIM:[190090]
About this Structure
1A1C is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Peptide ligands of pp60(c-src) SH2 domains: a thermodynamic and structural study., Charifson PS, Shewchuk LM, Rocque W, Hummel CW, Jordan SR, Mohr C, Pacofsky GJ, Peel MR, Rodriguez M, Sternbach DD, Consler TG, Biochemistry. 1997 May 27;36(21):6283-93. PMID:9174343
Page seeded by OCA on Mon Jun 30 15:46:44 2008
