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| | {{STRUCTURE_1n2y| PDB=1n2y | SCENE= }} | | {{STRUCTURE_1n2y| PDB=1n2y | SCENE= }} |
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| - | '''SOLUTION STRUCTURE OF SS-CYCLIZED CATESTATIN FRAGMENT FROM CHROMOGRANIN A'''
| + | ===SOLUTION STRUCTURE OF SS-CYCLIZED CATESTATIN FRAGMENT FROM CHROMOGRANIN A=== |
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| - | ==Overview==
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| - | Previous modeling (PDB 1cfk) of the catecholamine release-inhibitory "catestatin" region of chromogranin A (CgA) suggested a beta-strand/loop/beta-strand active conformation, displaying an electropositive Arg-rich loop (R(351)AR(353)GYGFR(358)). To explore this possibility, we studied NMR structures of linear and cyclic synthetic catestatin, bovine (bCgA(344-364)) or human (hCgA(352-372)). By 2-D (1)H-NMR, the structure of linear catestatin (hCgA(352-372)) exhibited the NOE pattern of a coiled loop (PDB 1lv4). We then constrained the structure, cyclizing the putative Arg-rich loop connecting the beta-strands: cyclic bCgA(350-362) ([C(0)]F(350)RARGYGFRGPGL(362)[C(+14)]). Favored conformations of cyclic bCgA(350-362) were determined by (1)H-NMR and (13)C-NMR spectroscopy. Cyclic bCgA(350-362) conformers (PDB 1n2y) adopted a "twisted-loop" conformation. Alignment between the homology model and the cyclic NMR structure showed that, while portions of the NMR structure's mid-molecule and carboxy-terminus were congruent with the homology model (RMSD, 1.61-1.91 A), the amino-terminal "twisted loop" coiled inward and away from the model (RMSD, 3.36 A). Constrained cyclic bCgA(350-362) did not exert nicotinic cholinergic antagonist activity (IC(50)>10 microM), when compared to full-length linear (IC(50) approximately 0.42-0.56 microM), or cyclic (IC(50) approximately 0.74 microM) catestatin. Thus, loss of activity in the small, constrained peptide did not result from either [Cys]-extension or cyclization, per se. While linear catestatin displays coiled character, a small cyclic derivative lost biological activity, perhaps because its amino-terminal domain deviated sharply from the predicted active conformation. These results refine the relationship between structure and function in catestatin, and suggest goals in future peptidomimetic syntheses, in particular attempts to constrain the correct amino-terminal shape for biological activity.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_14759560}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 14759560 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_14759560}} |
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| | ==About this Structure== | | ==About this Structure== |
| - | 1N2Y is a [[Single protein]] structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1krk 1krk]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N2Y OCA]. | + | 1N2Y is a [[Single protein]] structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1krk 1krk]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N2Y OCA]. |
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| | ==Reference== | | ==Reference== |
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| | [[Category: Tsigelny, I.]] | | [[Category: Tsigelny, I.]] |
| | [[Category: Catestatin choromogranin some]] | | [[Category: Catestatin choromogranin some]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 02:01:26 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 12:18:47 2008'' |
Revision as of 09:18, 28 July 2008
Template:STRUCTURE 1n2y
SOLUTION STRUCTURE OF SS-CYCLIZED CATESTATIN FRAGMENT FROM CHROMOGRANIN A
Template:ABSTRACT PUBMED 14759560
About this Structure
1N2Y is a Single protein structure. This structure supersedes the now removed PDB entry 1krk. Full experimental information is available from OCA.
Reference
Conformational preferences and activities of peptides from the catecholamine release-inhibitory (catestatin) region of chromogranin A., Preece NE, Nguyen M, Mahata M, Mahata SK, Mahapatra NR, Tsigelny I, O'Connor DT, Regul Pept. 2004 Apr 15;118(1-2):75-87. PMID:14759560
Page seeded by OCA on Mon Jul 28 12:18:47 2008
