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Structural re-alignment in an immunogenic surface region of ricin A chain.

Zemla AT, Ecale Zhou CL - Bioinform Biol Insights (2008)

Bottom Line: We compared structure alignments generated by several protein structure comparison programs to determine whether existing methods would satisfactorily align residues at a highly conserved position within an immunogenic loop in ribosome inactivating proteins (RIPs).Using default settings, structure alignments generated by several programs (CE, DaliLite, FATCAT, LGA, MAMMOTH, MATRAS, SHEBA, SSM) failed to align the respective conserved residues, although LGA reported correct residue-residue (R-R) correspondences when the beta-carbon (Cb) position was used as the point of reference in the alignment calculations.Results suggest that approaches to structure alignment employing alternate point representations corresponding to side chain position may yield structure alignments that are more consistent with observed conservation of functional surface residues than do standard alignment programs, which apply uniform criteria for alignment (i.e. alpha carbon (Ca) as point of reference) along the entirety of the peptide chain.

View Article: PubMed Central - PubMed

Affiliation: Computational Biology for Countermeasures Group, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.

ABSTRACT
We compared structure alignments generated by several protein structure comparison programs to determine whether existing methods would satisfactorily align residues at a highly conserved position within an immunogenic loop in ribosome inactivating proteins (RIPs). Using default settings, structure alignments generated by several programs (CE, DaliLite, FATCAT, LGA, MAMMOTH, MATRAS, SHEBA, SSM) failed to align the respective conserved residues, although LGA reported correct residue-residue (R-R) correspondences when the beta-carbon (Cb) position was used as the point of reference in the alignment calculations. Further tests using variable points of reference indicated that points distal from the beta carbon along a vector connecting the alpha and beta carbons yielded rigid structural alignments in which residues known to be highly conserved in RIPs were reported as corresponding residues in structural comparisons between ricin A chain, abrin-A, and other RIPs. Results suggest that approaches to structure alignment employing alternate point representations corresponding to side chain position may yield structure alignments that are more consistent with observed conservation of functional surface residues than do standard alignment programs, which apply uniform criteria for alignment (i.e. alpha carbon (Ca) as point of reference) along the entirety of the peptide chain. We present the results of tests that suggest the utility of allowing user-specified points of reference in generating alternate structural alignments, and we present a web server for automatically generating such alignments: http://as2ts.llnl.gov/AS2TS/LGA/lga_pdblist_plots.html.

No MeSH data available.


Related in: MedlinePlus

Sequence and structure alignments between ricin (1br6_A; Y91-T116) and abrin (1abr_A; Y85-S106). A) Summary of residue-residue (R-R) correspondences in a surface region containing a conserved aspartate (red). Column at right indicates programs and settings used to generate the correspondences (pink: sequence alignment programs, blue: structure alignment programs, orange: structure alignment calculated on Cb using LGA). Lower-case letters indicate residues that were not assigned correspondence, due to distance cutoffs being exceeded. For CLUSTALW and FUGUE calculations we used the sequences of 15 RIPs listed in Fig. 4. B) Detail of structural alignment between 1br6_A and 1abr_A generated using LGA on the beta-carbon setting. Orange: beta carbons of D96 (1br6_A), P95 (1br6_A) and D89 (1abr_A). A, B) Green: residues that produced consistent R-R correspondences regardless of alignment method used. Light or dark blue: residues that produced inconsistent R-R correspondences.
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f1-bbi-2008-005: Sequence and structure alignments between ricin (1br6_A; Y91-T116) and abrin (1abr_A; Y85-S106). A) Summary of residue-residue (R-R) correspondences in a surface region containing a conserved aspartate (red). Column at right indicates programs and settings used to generate the correspondences (pink: sequence alignment programs, blue: structure alignment programs, orange: structure alignment calculated on Cb using LGA). Lower-case letters indicate residues that were not assigned correspondence, due to distance cutoffs being exceeded. For CLUSTALW and FUGUE calculations we used the sequences of 15 RIPs listed in Fig. 4. B) Detail of structural alignment between 1br6_A and 1abr_A generated using LGA on the beta-carbon setting. Orange: beta carbons of D96 (1br6_A), P95 (1br6_A) and D89 (1abr_A). A, B) Green: residues that produced consistent R-R correspondences regardless of alignment method used. Light or dark blue: residues that produced inconsistent R-R correspondences.

Mentions: R-R correspondences derived from global alignments between the structures of abrin-A (1abr_A) and ricin A chain (1br6_A), generated by four sequence alignment programs (PSI-BLAST (Altschul et al. 1997) with five iterations on the NR non-redundant sequence database + a final iteration on PDB), Smith-Waterman (Smith and Waterman, 1981), CLUSTALW (Thompson et al. 1994)), FUGUE (Shi et al. 2001) and by eight structure comparison programs (CE (Shindyalov and Bourne, 1998); DaliLite (Holm and Park, 2000); FATCAT (Ye and Godzik, 2004); LGA (Zemla, 2003); MAMMOTH (Olmea et al. 2002); MATRAS (Kawabata, 2003); SSM (Krissenel and Henrick, 2004); SHEBA (Jung and Lee, 2000)) were compared to determine whether the highly conserved aspartate residues (D89/D96) would be assigned corresponding positions by any of the alignment programs (Fig. 1).


Structural re-alignment in an immunogenic surface region of ricin A chain.

Zemla AT, Ecale Zhou CL - Bioinform Biol Insights (2008)

Sequence and structure alignments between ricin (1br6_A; Y91-T116) and abrin (1abr_A; Y85-S106). A) Summary of residue-residue (R-R) correspondences in a surface region containing a conserved aspartate (red). Column at right indicates programs and settings used to generate the correspondences (pink: sequence alignment programs, blue: structure alignment programs, orange: structure alignment calculated on Cb using LGA). Lower-case letters indicate residues that were not assigned correspondence, due to distance cutoffs being exceeded. For CLUSTALW and FUGUE calculations we used the sequences of 15 RIPs listed in Fig. 4. B) Detail of structural alignment between 1br6_A and 1abr_A generated using LGA on the beta-carbon setting. Orange: beta carbons of D96 (1br6_A), P95 (1br6_A) and D89 (1abr_A). A, B) Green: residues that produced consistent R-R correspondences regardless of alignment method used. Light or dark blue: residues that produced inconsistent R-R correspondences.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2735970&req=5

f1-bbi-2008-005: Sequence and structure alignments between ricin (1br6_A; Y91-T116) and abrin (1abr_A; Y85-S106). A) Summary of residue-residue (R-R) correspondences in a surface region containing a conserved aspartate (red). Column at right indicates programs and settings used to generate the correspondences (pink: sequence alignment programs, blue: structure alignment programs, orange: structure alignment calculated on Cb using LGA). Lower-case letters indicate residues that were not assigned correspondence, due to distance cutoffs being exceeded. For CLUSTALW and FUGUE calculations we used the sequences of 15 RIPs listed in Fig. 4. B) Detail of structural alignment between 1br6_A and 1abr_A generated using LGA on the beta-carbon setting. Orange: beta carbons of D96 (1br6_A), P95 (1br6_A) and D89 (1abr_A). A, B) Green: residues that produced consistent R-R correspondences regardless of alignment method used. Light or dark blue: residues that produced inconsistent R-R correspondences.
Mentions: R-R correspondences derived from global alignments between the structures of abrin-A (1abr_A) and ricin A chain (1br6_A), generated by four sequence alignment programs (PSI-BLAST (Altschul et al. 1997) with five iterations on the NR non-redundant sequence database + a final iteration on PDB), Smith-Waterman (Smith and Waterman, 1981), CLUSTALW (Thompson et al. 1994)), FUGUE (Shi et al. 2001) and by eight structure comparison programs (CE (Shindyalov and Bourne, 1998); DaliLite (Holm and Park, 2000); FATCAT (Ye and Godzik, 2004); LGA (Zemla, 2003); MAMMOTH (Olmea et al. 2002); MATRAS (Kawabata, 2003); SSM (Krissenel and Henrick, 2004); SHEBA (Jung and Lee, 2000)) were compared to determine whether the highly conserved aspartate residues (D89/D96) would be assigned corresponding positions by any of the alignment programs (Fig. 1).

Bottom Line: We compared structure alignments generated by several protein structure comparison programs to determine whether existing methods would satisfactorily align residues at a highly conserved position within an immunogenic loop in ribosome inactivating proteins (RIPs).Using default settings, structure alignments generated by several programs (CE, DaliLite, FATCAT, LGA, MAMMOTH, MATRAS, SHEBA, SSM) failed to align the respective conserved residues, although LGA reported correct residue-residue (R-R) correspondences when the beta-carbon (Cb) position was used as the point of reference in the alignment calculations.Results suggest that approaches to structure alignment employing alternate point representations corresponding to side chain position may yield structure alignments that are more consistent with observed conservation of functional surface residues than do standard alignment programs, which apply uniform criteria for alignment (i.e. alpha carbon (Ca) as point of reference) along the entirety of the peptide chain.

View Article: PubMed Central - PubMed

Affiliation: Computational Biology for Countermeasures Group, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.

ABSTRACT
We compared structure alignments generated by several protein structure comparison programs to determine whether existing methods would satisfactorily align residues at a highly conserved position within an immunogenic loop in ribosome inactivating proteins (RIPs). Using default settings, structure alignments generated by several programs (CE, DaliLite, FATCAT, LGA, MAMMOTH, MATRAS, SHEBA, SSM) failed to align the respective conserved residues, although LGA reported correct residue-residue (R-R) correspondences when the beta-carbon (Cb) position was used as the point of reference in the alignment calculations. Further tests using variable points of reference indicated that points distal from the beta carbon along a vector connecting the alpha and beta carbons yielded rigid structural alignments in which residues known to be highly conserved in RIPs were reported as corresponding residues in structural comparisons between ricin A chain, abrin-A, and other RIPs. Results suggest that approaches to structure alignment employing alternate point representations corresponding to side chain position may yield structure alignments that are more consistent with observed conservation of functional surface residues than do standard alignment programs, which apply uniform criteria for alignment (i.e. alpha carbon (Ca) as point of reference) along the entirety of the peptide chain. We present the results of tests that suggest the utility of allowing user-specified points of reference in generating alternate structural alignments, and we present a web server for automatically generating such alignments: http://as2ts.llnl.gov/AS2TS/LGA/lga_pdblist_plots.html.

No MeSH data available.


Related in: MedlinePlus