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| Phylogeny of the serpin superfamily: Implications of patterns of amino acid conservation for structure and function |
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| Author(s): Irving JA, Pike RN, Lesk AM, Whisstock JC |
| Source: GENOME RESEARCH Volume: 10 Issue: 12 Pages: 1845-1864 Published: DEC 2000 |
| Times Cited: 182 References: 134 |
| Abstract: We present a comprehensive alignment and phylogenetic analysis of the serpins, a superfamily of proteins with known members in higher animals, nematodes, insects, plants, and viruses. We analyze, compare, and classify 219 proteins representative of eight major and eight minor subfamilies, using a novel technique of consensus analysis. Patterns of sequence conservation characterize the family as a whole, with a clear relationship to the mechanism of function. Variations of these patterns within phylogenetically distinct groups can be correlated with the divergence of structure and function. The goals of this work are to provide a carefully curated alignment of serpin sequences, to describe patterns of conservation and divergence, and to derive a phylogenetic tree expressing the relationships among the members of this family. We extend earlier studies by Huber and Carrell as well as by Marshall, after whose publication the serpin family has grown functionally, taxonomically, and structurally. We used gene and protein sequence data, crystal structures, and chromosomal location where available. The results illuminate structure-function relationships in serpins, suggesting roles for conserved residues in the mechanism of conformational change. The phylogeny provides a rational evolutionary framework to classify serpins and enables identification of conserved amino acids. Patterns of conservation also provide an initial point of comparison for genes identified by the various genome projects. New homologs emerging from sequencing projects can either take their place within the current classification or, if necessary, extend it. |
| Document Type: Review |
| Language: English |
| Reprint Address: Whisstock, JC (reprint author), Monash Univ, Dept Biochem & Mol Biol, Clayton Campus, Melbourne, Vic 3168 Australia |
Addresses:
1. Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic 3168 Australia
2. Univ Cambridge, Sch Clin, Cambridge Inst Med Res, Wellcome Trust Ctr Study Mol Mechanisms Dis, Cambridge CB2 2XY, England |
| Publisher: COLD SPRING HARBOR LAB PRESS, 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA |
| Subject Category: Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity |
| IDS Number: 382QN |
| ISSN: 1088-9051 |
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