Sanishvili_2003_J.Biol.Chem_278_26039

Reference

Title : Integrating structure, bioinformatics, and enzymology to discover function: BioH, a new carboxylesterase from Escherichia coli - Sanishvili_2003_J.Biol.Chem_278_26039
Author(s) : Sanishvili R , Yakunin AF , Laskowski RA , Skarina T , Evdokimova E , Doherty-Kirby A , Lajoie GA , Thornton JM , Arrowsmith CH , Savchenko A , Joachimiak A , Edwards AM
Ref : Journal of Biological Chemistry , 278 :26039 , 2003
Abstract :

Structural proteomics projects are generating three-dimensional structures of novel, uncharacterized proteins at an increasing rate. However, structure alone is often insufficient to deduce the specific biochemical function of a protein. Here we determined the function for a protein using a strategy that integrates structural and bioinformatics data with parallel experimental screening for enzymatic activity. BioH is involved in biotin biosynthesis in Escherichia coli and had no previously known biochemical function. The crystal structure of BioH was determined at 1.7 A resolution. An automated procedure was used to compare the structure of BioH with structural templates from a variety of different enzyme active sites. This screen identified a catalytic triad (Ser82, His235, and Asp207) with a configuration similar to that of the catalytic triad of hydrolases. Analysis of BioH with a panel of hydrolase assays revealed a carboxylesterase activity with a preference for short acyl chain substrates. The combined use of structural bioinformatics with experimental screens for detecting enzyme activity could greatly enhance the rate at which function is determined from structure.

PubMedSearch : Sanishvili_2003_J.Biol.Chem_278_26039
PubMedID: 12732651
Gene_locus related to this paper: ecoli-bioh

Related information

Inhibitor PMSF
Gene_locus PMSF    ecoli-bioh
Family PMSF    ecoli-bioh    BioH
Structure PMSF    ecoli-bioh    BioH    1M33

Citations formats

Sanishvili R, Yakunin AF, Laskowski RA, Skarina T, Evdokimova E, Doherty-Kirby A, Lajoie GA, Thornton JM, Arrowsmith CH, Savchenko A, Joachimiak A, Edwards AM (2003)
Integrating structure, bioinformatics, and enzymology to discover function: BioH, a new carboxylesterase from Escherichia coli
Journal of Biological Chemistry 278 :26039

Sanishvili R, Yakunin AF, Laskowski RA, Skarina T, Evdokimova E, Doherty-Kirby A, Lajoie GA, Thornton JM, Arrowsmith CH, Savchenko A, Joachimiak A, Edwards AM (2003)
Journal of Biological Chemistry 278 :26039