Research article summary (published 22 Sep 2009):

Structural relationships among proteins with different global topologies and their implications for function annotation strategies.

Full Abstract

It has become increasingly apparent that geometric relationships often exist between regions of two proteins that have quite different global topologies or folds. In this article, we examine whether such relationships can be used to infer a functional connection between the two proteins in question. We find, by considering a number of examples involving metal and cation binding, sugar binding, and aromatic group binding, that geometrically similar protein fragments can share related functions, even if they have been classified as belonging to different folds and topologies. Thus, the use of classifications inevitably limits the number of functional inferences that can be obtained from the comparative analysis of protein structures. In contrast, the development of interactive computational tools that recognize the "continuous" nature of protein structure/function space, by increasing the number of potentially meaningful relationships that are considered, may offer a dramatic enhancement in the ability to extract information from protein structure databases. We introduce the MarkUs server, that embodies this strategy and that is designed for a user interested in developing and validating specific functional hypotheses.

Author information

Author/s: Petrey, Donald (D); Fischer, Markus (M); Honig, Barry (B);

Affiliation: Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Center for Computational Biology and Bioinformatics, Columbia University, 1130 St. Nicholas Avenue, Room 815, New York, NY 10032, USA.

Grants: CA121852 (Agency:NCI NIH HHS) ; GM030518 (Agency:NIGMS NIH HHS) ; GM074958 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A), published in United States. (Language: eng)

Reference: 2009-Oct; vol 106 (issue 41) : pp 17377-82

Dates: Created 2009/10/15; Completed 2009/11/03; Revised 2009/11/06;

PMID: 19805138, status: MEDLINE (last retrieval date: 11/9/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amino Acid Sequence Binding Sites Carbohydrate Metabolism Databases, Factual Mathematics Models, Molecular

Peptide Fragments - chemistry; metabolism Protein Binding Protein Conformation Proteins - chemistry; classification; metabolism Sequence Alignment Sequence Homology, Amino Acid

Associated Chemicals: Peptide Fragments (0) ; Proteins (0)

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