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Structural relationships among proteins with different global topologies and their implications for function annotation strategies
被引:61
作者:
Petrey, Donald
[1
]
Fischer, Markus
[1
]
Honig, Barry
[1
]
机构:
[1] Columbia Univ, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA
来源:
基金:
美国国家卫生研究院;
关键词:
protein fold space;
protein function annotation;
protein structure alignment;
protein structure similarity;
FOLD SPACE;
CATH DATABASE;
EVOLUTION;
SEQUENCE;
ALIGNMENTS;
CLASSIFICATION;
IDENTIFICATION;
SUPERFAMILIES;
PREDICTION;
HOMOLOGY;
D O I:
10.1073/pnas.0907971106
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
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.
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页码:17377 / 17382
页数:6
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