Vincent_2003_J.Mol.Biol_330_593

Reference

Title : Multifunctional Xylooligosaccharide\/Cephalosporin C Deacetylase Revealed by the Hexameric Structure of the Bacillus subtilis Enzyme at 1.9A Resolution - Vincent_2003_J.Mol.Biol_330_593
Author(s) : Vincent F , Charnock SJ , Verschueren KH , Turkenburg JP , Scott DJ , Offen WA , Roberts S , Pell G , Gilbert HJ , Davies GJ , Brannigan JA
Ref : Journal of Molecular Biology , 330 :593 , 2003
Abstract :

Esterases and deacetylases active on carbohydrate ligands have been classified into 14 families based upon amino acid sequence similarities. Enzymes from carbohydrate esterase family seven (CE-7) are unusual in that they display activity towards both acetylated xylooligosaccharides and the antibiotic, cephalosporin C. The 1.9A structure of the multifunctional CE-7 esterase (hereinafter CAH) from Bacillus subtilis 168 reveals a classical alpha/beta hydrolase fold encased within a 32 hexamer. This is the first example of a hexameric alpha/beta hydrolase and is further evidence of the versatility of this particular fold, which is used in a wide variety of biological contexts. A narrow entrance tunnel leads to the centre of the molecule, where the six active-centre catalytic triads point towards the tunnel interior and thus are sequestered away from cytoplasmic contents. By analogy to self-compartmentalising proteases, the tunnel entrance may function to hinder access of large substrates to the poly-specific active centre. This would explain the observation that the enzyme is active on a variety of small, acetylated molecules. The structure of an active site mutant in complex with the reaction product, acetate, reveals details of the putative oxyanion binding site, and suggests that substrates bind predominantly through non-specific contacts with protein hydrophobic residues. Protein residues involved in catalysis are tethered by interactions with protein excursions from the canonical alpha/beta hydrolase fold. These excursions also mediate quaternary structure maintenance, so it would appear that catalytic competence is only achieved on protein multimerisation. We suggest that the acetyl xylan esterase (EC 3.1.1.72) and cephalosporin C deacetylase (EC 3.1.1.41) enzymes of the CE-7 family represent a single class of proteins with a multifunctional deacetylase activity against a range of small substrates.

PubMedSearch : Vincent_2003_J.Mol.Biol_330_593
PubMedID: 12842474
Gene_locus related to this paper: bacsu-CAH

Related information

Substrate Acetate
Gene_locus Acetate    bacsu-CAH
Family Acetate    bacsu-CAH    Acetyl-esterase_deacetylase
Structure Acetate    bacsu-CAH    Acetyl-esterase_deacetylase    1ODS    1ODT

Citations formats

Vincent F, Charnock SJ, Verschueren KH, Turkenburg JP, Scott DJ, Offen WA, Roberts S, Pell G, Gilbert HJ, Davies GJ, Brannigan JA (2003)
Multifunctional Xylooligosaccharide\/Cephalosporin C Deacetylase Revealed by the Hexameric Structure of the Bacillus subtilis Enzyme at 1.9A Resolution
Journal of Molecular Biology 330 :593

Vincent F, Charnock SJ, Verschueren KH, Turkenburg JP, Scott DJ, Offen WA, Roberts S, Pell G, Gilbert HJ, Davies GJ, Brannigan JA (2003)
Journal of Molecular Biology 330 :593