The structure of Rv3717 reveals a novel amidase from Mycobacterium tuberculosis. (1st December 2013)

• Record Type: Journal Article
• Authors: Kumar, Atul; Kumar, Sanjiv; Kumar, Dilip; Mishra, Arpit; Dewangan, Rikeshwer P.; Shrivastava, Priyanka; Ramachandran, Srinivasan; Taneja, Bhupesh
• Is Part Of: Acta crystallographica. Volume 69:Part 12(2013:Dec.)
• Page Start: 2543
• Page End: 2554
• Publication Date: 2013-12-01
• Subjects: Biomolecules -- Structure -- Periodicals; Physical biochemistry -- Periodicals; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; 572
• DOI: 10.1107/S0907444913026371
• Languages: English
• ISSNs: 0907-4449

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Bacterial <italic>N</italic>‐acetylmuramoyl‐L‐alanine amidases are cell‐wall hydrolases that hydrolyze the bond between <italic>N</italic>‐acetylmuramic acid and L‐alanine in cell‐wall glycopeptides. Rv3717 of <italic>Mycobacterium tuberculosis</italic> has been identified as a unique autolysin that lacks a cell‐wall‐binding domain (CBD) and its structure has been determined to 1.7 Å resolution by the Pt‐SAD phasing method. Rv3717 possesses an α/β‐fold and is a zinc‐dependent hydrolase. The structure reveals a short flexible hairpin turn that partially occludes the active site and may be involved in autoregulation. This type of autoregulation of activity of PG hydrolases has been observed in <italic>Bartonella henselae</italic> amidase (AmiB) and may be a general mechanism used by some of the redundant amidases to regulate cell‐wall hydrolase activity in bacteria. Rv3717 utilizes its net positive charge for substrate binding and exhibits activity towards a broad spectrum of substrate cell walls. The enzymatic activity of Rv3717 was confirmed by isolation and identification of its enzymatic products by LC/MS. These studies indicate that Rv3717, an <italic>N</italic>‐acetylmuramoyl‐L‐alanine amidase from <italic>M. tuberculosis</italic>, represents a new family of lytic amidases that do not have a separate CBD and are regulated conformationally.</p> </abstract>