1t8j
From Proteopedia
(New page: 200px<br /><applet load="1t8j" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t8j" /> '''NMR Structure of BBA5, A Compact, Independen...) |
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| - | [[Image:1t8j.jpg|left|200px]]<br /><applet load="1t8j" size=" | + | [[Image:1t8j.jpg|left|200px]]<br /><applet load="1t8j" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1t8j" /> | caption="1t8j" /> | ||
'''NMR Structure of BBA5, A Compact, Independently Folded BBA Motif'''<br /> | '''NMR Structure of BBA5, A Compact, Independently Folded BBA Motif'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Small folded polypeptide motifs represented highly simplified | + | BACKGROUND: Small folded polypeptide motifs represented highly simplified systems for theoretical and experimental studies on protein structure and folding. We have recently reported the design and characterization of a metal-ion-independent 23-residue peptide with a beta beta alpha structure (BBA1), based on the zinc finger domains. To understand better the determinants of structure for this small peptide, we investigated the conformational role of the synthetic residue 3-(1, 10-phenanthrol-2-yl)-L-alanine (Fen) in BBA1. RESULTS: NMR analysis revealed that replacing the Fen residue of peptide BBA1 by either of the natural amino acids tyrosine (BBA2) or tryptophan (BBA3) resulted in conformational flexibility in the sheet and loop regions of the structure. This conformational ambiguity was eliminated in peptides BBA4 and BBA5 by including charged residues on the exterior of the beta hairpin designed to both select against the undesired fold and stabilize the desired structure. The evaluation of two additional peptides (BBA6 and BBA7) provided further insight into the specific involvement of the surface polar residues in the creation of well-defined structure in BBA4 and BBA5. The sequences of BBA5, BBA6 and BBA7 include only one non-standard amino acid (D-proline), which constrains a critical engineered type II' turn. CONCLUSIONS: Manipulation of residues on the exterior of small beta beta alpha motifs has led to the design of 23-residue polypeptides that adopt a defined tertiary structure in the absence of synthetic amino acids, increasing the availability and expanding the potential uses of the BBA motif. The importance of negative design concepts to the creation of structured polypeptides is also highlighted. |
==About this Structure== | ==About this Structure== | ||
| - | 1T8J is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with ACE and NH2 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1T8J is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=ACE:'>ACE</scene> and <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T8J OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Imperiali, B.]] | [[Category: Imperiali, B.]] | ||
| - | [[Category: Ottesen, J | + | [[Category: Ottesen, J J.]] |
| - | [[Category: Struthers, M | + | [[Category: Struthers, M D.]] |
[[Category: ACE]] | [[Category: ACE]] | ||
[[Category: NH2]] | [[Category: NH2]] | ||
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[[Category: protein design]] | [[Category: protein design]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:11:03 2008'' |
Revision as of 13:11, 21 February 2008
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NMR Structure of BBA5, A Compact, Independently Folded BBA Motif
Overview
BACKGROUND: Small folded polypeptide motifs represented highly simplified systems for theoretical and experimental studies on protein structure and folding. We have recently reported the design and characterization of a metal-ion-independent 23-residue peptide with a beta beta alpha structure (BBA1), based on the zinc finger domains. To understand better the determinants of structure for this small peptide, we investigated the conformational role of the synthetic residue 3-(1, 10-phenanthrol-2-yl)-L-alanine (Fen) in BBA1. RESULTS: NMR analysis revealed that replacing the Fen residue of peptide BBA1 by either of the natural amino acids tyrosine (BBA2) or tryptophan (BBA3) resulted in conformational flexibility in the sheet and loop regions of the structure. This conformational ambiguity was eliminated in peptides BBA4 and BBA5 by including charged residues on the exterior of the beta hairpin designed to both select against the undesired fold and stabilize the desired structure. The evaluation of two additional peptides (BBA6 and BBA7) provided further insight into the specific involvement of the surface polar residues in the creation of well-defined structure in BBA4 and BBA5. The sequences of BBA5, BBA6 and BBA7 include only one non-standard amino acid (D-proline), which constrains a critical engineered type II' turn. CONCLUSIONS: Manipulation of residues on the exterior of small beta beta alpha motifs has led to the design of 23-residue polypeptides that adopt a defined tertiary structure in the absence of synthetic amino acids, increasing the availability and expanding the potential uses of the BBA motif. The importance of negative design concepts to the creation of structured polypeptides is also highlighted.
About this Structure
1T8J is a Protein complex structure of sequences from [1] with and as ligands. Full crystallographic information is available from OCA.
Reference
Design and NMR analyses of compact, independently folded BBA motifs., Struthers M, Ottesen JJ, Imperiali B, Fold Des. 1998;3(2):95-103. PMID:9565754
Page seeded by OCA on Thu Feb 21 15:11:03 2008
