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J. Biol. Chem., Vol. 281, Issue 43, 32516-32525, October 27, 2006

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Structural and Functional Analysis of a Conjugated Bile Salt Hydrolase from Bifidobacterium longum Reveals an Evolutionary Relationship with Penicillin V Acylase^*

R. Suresh Kumar¹, James A. Brannigan², Asmita A. Prabhune, Archana V. Pundle, Guy G. Dodson, Eleanor J. Dodson, and C. G. Suresh³

From the Division of Biochemical Sciences, National Chemical Laboratory, Pune 411 008, India and the Structural Biology Laboratory, Department of Chemistry, University of York, York YO10 5YW, United Kingdom

Bile salt hydrolase (BSH) is an enzyme produced by the intestinal microflora that catalyzes the deconjugation of glycine- or taurine-linked bile salts. The crystal structure of BSH reported here from Bifidobacterium longum reveals that it is a member of N-terminal nucleophil hydrolase structural superfamily possessing the characteristic tetra-lamellar tertiary structure arrangement. Site-directed mutagenesis of the catalytic nucleophil residue, however, shows that it has no role in zymogen processing into its corresponding active form. Substrate specificity was studied using Michaelis-Menten and inhibition kinetics and fluorescence spectroscopy. These data were compared with the specificity profile of BSH from Clostridium perfrigens and pencillin V acylase from Bacillus sphaericus, for both of which the three-dimensional structures are available. Comparative analysis shows a gradation in activity toward common substrates, throwing light on a possible common route toward the evolution of pencillin V acylase and BSH.

Received for publication, May 2, 2006 , and in revised form, July 19, 2006.

The atomic coordinates and structure factors (codes 2HEZ and 2HF0) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2 and Table S1.

¹ Supported by a Council of Scientific and Industrial Research (CSIR, New Delhi) Senior Research Fellowship.

² Supported by the Wellcome Trust. To whom correspondence may be addressed. E-mail: jab{at}ysbl.york.ac.uk.

³ To whom correspondence may be addressed. Tel.: 91-20-25902236; Fax: 91-20-25902648; E-mail: cg.suresh{at}ncl.res.in.

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