Cited by 126Protein Structure and DynamicsEnzyme Structure and FunctionGenomics and Phylogenetic Studies

Sequence‐similar, structure‐dissimilar protein pairs in the PDB

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Kosloff, Mickey, Kolodny, Rachel·2008·Proteins: Structure, Function, and Bioinformatics

Abstract

It is often assumed that in the Protein Data Bank (PDB), two proteins with similar sequences will also have similar structures. Accordingly, it has proved useful to develop subsets of the PDB from which “redundant” structures have been removed, based on a sequence‐based criterion for similarity. Similarly, when predicting protein structure using homology modeling, if a template structure for modeling a target sequence is selected by sequence alone, this implicitly assumes that all sequence‐similar templates are equivalent. Here, we show that this assumption is often not correct and that standard approaches to create subsets of the PDB can lead to the loss of structurally and functionally important information. We have carried out sequence‐based structural superpositions and geometry‐based structural alignments of a large number of protein pairs to determine the extent to which sequence similarity ensures structural similarity. We find many examples where two proteins that are similar in sequence have structures that differ significantly from one another. The source of the structural differences usually has a functional basis. The number of such proteins pairs that are identified and the magnitude of the dissimilarity depend on the approach that is used to calculate the differences; in particular sequence‐based structure superpositioning will identify a larger number of structurally dissimilar pairs than geometry‐based structural alignments. When two sequences can be aligned in a statistically meaningful way, sequence‐based structural superpositioning provides a meaningful measure of structural differences. This approach and geometry‐based structure alignments reveal somewhat different information and one or the other might be preferable in a given application. Our results suggest that in some cases, notably homology modeling, the common use of nonredundant datasets, culled from the PDB based on sequence, may mask important structural and functional information. We have established a data base of sequence‐similar, structurally dissimilar protein pairs that will help address this problem (http://luna.bioc.columbia.edu/rachel/seqsimstrdiff.htm). Proteins 2008. © 2007 Wiley‐Liss, Inc.

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  • There are examples of highly similar protein sequences having radically different structures and functions and of sequences that can form multiple folds.

    “Although it is generally believed that proteins with similar sequences form similar structures, there are also interesting examples of highly similar protein sequences having radically different structures and functions 60,61 and of sequences that can form multiple folds 62.”

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Authors
Kosloff, M., & Kolodny, R.
Affiliations
  • Duke Medical Center (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Kosloff, Mickey
Venue
Proteins: Structure, Function, and Bioinformatics
Publisher
Wiley
Published
2007-11-14
Volume
71
Issue
2
Pages
891-902
ISSN
  • 0887-3585 (ISSN-L)
  • 1097-0134
OpenAlex
W2131204071
Cited by
124
References
48
Citations by year
2026: 5 · 2025: 6 · 2024: 8 · 2023: 6 · 2022: 6 · 2021: 11 · 2020: 9 · 2019: 6 · 2018: 10 · 2017: 9 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 5 · 2012: 4
FWCI
2.52
Type
journal article
Language
en
Open access
Locations
  • Proteins Structure Function and Bioinformatics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords
protein structural similarity, protein function
MeSH terms
Models, Molecular, Sequence Alignment, Protein Structure, Tertiary, Databases, Protein

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