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PMID: 19472362 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Evolutionary constraints on structural similarity in orthologs and paralogs.

Protein science : a publication of the Protein Society ·Vol. 18 ·No. 6 ·2009-06-00 ·Pages 1306-15

Peterson ME, Chen F, Saven JG, Roos DS, Babbitt PC, Sali A

Abstract

Although a quantitative relationship between sequence similarity and structural similarity has long been established, little is known about the impact of orthology on the relationship between protein sequence and structure. Among homologs, orthologs (derived by speciation) more frequently have similar functions than paralogs (derived by duplication). Here, we hypothesize that an orthologous pair will tend to exhibit greater structural similarity than a paralogous pair at the same level of sequence similarity. To test this hypothesis, we used 284,459 pairwise structure-based alignments of 12,634 unique domains from SCOP as well as orthology and paralogy assignments from OrthoMCL DB. We divided the comparisons by sequence identity and determined whether the sequence-structure relationship differed between the orthologs and paralogs. We found that at levels of sequence identity between 30 and 70%, orthologous domain pairs indeed tend to be significantly more structurally similar than paralogous pairs at the same level of sequence identity. An even larger difference is found when comparing ligand binding residues instead of whole domains. These differences between orthologs and paralogs are expected to be useful for selecting template structures in comparative modeling and target proteins in structural genomics.

MeSH Terms
Amino Acid Sequence Databases, Protein Evolution, Molecular Protein Structure, Tertiary Proteins/chemistry Sequence Alignment Structure-Activity Relationship
Chemicals
Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Peterson Mark E
Department of Bioengineering and Therapeutic Sciences, University of California-San Francisco, 1700 4th Street, San Francisco, CA 94158, USA. [email protected]
Chen Feng
Saven Jeffery G
Roos David S
Babbitt Patricia C
Sali Andrej
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Article Info
Journal
Protein science : a publication of the Protein Society
Abbr.
Protein Sci
ISSN
1469-896X
DOI
10.1002/pro.143
Email
[email protected]
Published
2009-06-00
Pages
1306-15
Language
English
Region
United States
NLM ID
9211750
PMCID
PMC2774440
Subset
IM
Grants
NIGMS NIH HHS · P01 GM071790 · United States
NIGMS NIH HHS · P01 GM 71790 · United States
NIGMS NIH HHS · R01 GM 54762 · United States
NIGMS NIH HHS · R01 GM 60595 · United States
NIGMS NIH HHS · R01 GM 61267 · United States
NIGMS NIH HHS · U54 GM 074945 · United States
External Links
PubMed source DOI: 10.1002/pro.143 PMC Full Text View journal details
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