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Observation of glycine zipper and unanticipated occurrence of ambidextrous helices in the crystal structure of a chiral undecapeptide
BACKGROUND: The de novo design of peptides and proteins has recently surfaced as an approach for investigating protein structure and function. This approach vitally tests our knowledge of protein folding and function, while also laying the groundwork for the fabrication of proteins with properties n...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042501/ https://www.ncbi.nlm.nih.gov/pubmed/17678528 http://dx.doi.org/10.1186/1472-6807-7-51 |
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author | Acharya, Rudresh Gupta, Madhvi Ramakumar, Suryanarayanarao Ramagopal, Udupi A Chauhan, Virander S |
author_facet | Acharya, Rudresh Gupta, Madhvi Ramakumar, Suryanarayanarao Ramagopal, Udupi A Chauhan, Virander S |
author_sort | Acharya, Rudresh |
collection | PubMed |
description | BACKGROUND: The de novo design of peptides and proteins has recently surfaced as an approach for investigating protein structure and function. This approach vitally tests our knowledge of protein folding and function, while also laying the groundwork for the fabrication of proteins with properties not precedented in nature. The success of these studies relies heavily on the ability to design relatively short peptides that can espouse stable secondary structures. To this end, substitution with α, β-dehydroamino acids, especially α, β-dehydrophenylalanine (ΔPhe) comes in use for spawning well-defined structural motifs. Introduction of ΔPhe induces β-bends in small and 3(10)-helices in longer peptide sequences. RESULTS: The present report is an investigation of the effect of incorporating two glycines in the middle of a ΔPhe containing undecapeptide. A de novo designed undecapeptide, Ac-Gly(1)-Ala(2)-ΔPhe(3)-Leu(4)-Gly(5)-ΔPhe(6)-Leu(7)-Gly(8)-ΔPhe(9)-Ala(10)-Gly(11)-NH(2), was synthesized and characterized using X-ray diffraction and Circular Dichroism spectroscopic methods. Crystallographic studies suggest that, despite the presence of L-amino acid (L-Ala and L-Leu) residues in the middle of the sequence, the peptide adopts a 3(10)-helical conformation of ambidextrous screw sense, one of them a left-handed (A) and the other a right-handed (B) 3(10)-helix with A and B being antiparallel to each other. However, CD studies reveal that the undecapeptide exclusively adopts a right-handed 3(10)-helical conformation. In the crystal packing, three different interhelical interfaces, Leu-Leu, Gly-Gly and ΔPhe-ΔPhe are observed between the helices A and B. A network of C-H...O hydrogen bonds are observed at ΔPhe-ΔPhe and Gly-Gly interhelical interfaces. An important feature observed is the occurrence of glycine zipper motif at Gly-Gly interface. At this interface, the geometric pattern of interhelical interactions seems to resemble those observed between helices in transmembrane (TM) proteins. CONCLUSION: The present design strategy can thus be exploited in future work on de novo design of helical bundles of higher order and compaction utilizing ΔPhe residues along with GXXG motif. |
format | Text |
id | pubmed-2042501 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-20425012007-10-26 Observation of glycine zipper and unanticipated occurrence of ambidextrous helices in the crystal structure of a chiral undecapeptide Acharya, Rudresh Gupta, Madhvi Ramakumar, Suryanarayanarao Ramagopal, Udupi A Chauhan, Virander S BMC Struct Biol Research Article BACKGROUND: The de novo design of peptides and proteins has recently surfaced as an approach for investigating protein structure and function. This approach vitally tests our knowledge of protein folding and function, while also laying the groundwork for the fabrication of proteins with properties not precedented in nature. The success of these studies relies heavily on the ability to design relatively short peptides that can espouse stable secondary structures. To this end, substitution with α, β-dehydroamino acids, especially α, β-dehydrophenylalanine (ΔPhe) comes in use for spawning well-defined structural motifs. Introduction of ΔPhe induces β-bends in small and 3(10)-helices in longer peptide sequences. RESULTS: The present report is an investigation of the effect of incorporating two glycines in the middle of a ΔPhe containing undecapeptide. A de novo designed undecapeptide, Ac-Gly(1)-Ala(2)-ΔPhe(3)-Leu(4)-Gly(5)-ΔPhe(6)-Leu(7)-Gly(8)-ΔPhe(9)-Ala(10)-Gly(11)-NH(2), was synthesized and characterized using X-ray diffraction and Circular Dichroism spectroscopic methods. Crystallographic studies suggest that, despite the presence of L-amino acid (L-Ala and L-Leu) residues in the middle of the sequence, the peptide adopts a 3(10)-helical conformation of ambidextrous screw sense, one of them a left-handed (A) and the other a right-handed (B) 3(10)-helix with A and B being antiparallel to each other. However, CD studies reveal that the undecapeptide exclusively adopts a right-handed 3(10)-helical conformation. In the crystal packing, three different interhelical interfaces, Leu-Leu, Gly-Gly and ΔPhe-ΔPhe are observed between the helices A and B. A network of C-H...O hydrogen bonds are observed at ΔPhe-ΔPhe and Gly-Gly interhelical interfaces. An important feature observed is the occurrence of glycine zipper motif at Gly-Gly interface. At this interface, the geometric pattern of interhelical interactions seems to resemble those observed between helices in transmembrane (TM) proteins. CONCLUSION: The present design strategy can thus be exploited in future work on de novo design of helical bundles of higher order and compaction utilizing ΔPhe residues along with GXXG motif. BioMed Central 2007-08-01 /pmc/articles/PMC2042501/ /pubmed/17678528 http://dx.doi.org/10.1186/1472-6807-7-51 Text en Copyright © 2007 Acharya et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Acharya, Rudresh Gupta, Madhvi Ramakumar, Suryanarayanarao Ramagopal, Udupi A Chauhan, Virander S Observation of glycine zipper and unanticipated occurrence of ambidextrous helices in the crystal structure of a chiral undecapeptide |
title | Observation of glycine zipper and unanticipated occurrence of ambidextrous helices in the crystal structure of a chiral undecapeptide |
title_full | Observation of glycine zipper and unanticipated occurrence of ambidextrous helices in the crystal structure of a chiral undecapeptide |
title_fullStr | Observation of glycine zipper and unanticipated occurrence of ambidextrous helices in the crystal structure of a chiral undecapeptide |
title_full_unstemmed | Observation of glycine zipper and unanticipated occurrence of ambidextrous helices in the crystal structure of a chiral undecapeptide |
title_short | Observation of glycine zipper and unanticipated occurrence of ambidextrous helices in the crystal structure of a chiral undecapeptide |
title_sort | observation of glycine zipper and unanticipated occurrence of ambidextrous helices in the crystal structure of a chiral undecapeptide |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042501/ https://www.ncbi.nlm.nih.gov/pubmed/17678528 http://dx.doi.org/10.1186/1472-6807-7-51 |
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