Crystal structure of uncleaved L-aspartate-α-decarboxylase from Mycobacterium tuberculosis
Gopalan, G. Chopra, S. Ranganathan, A. Swaminathan, K.
Gopalan, G.
Chopra, S.
Ranganathan, A.
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Alternative Title
Abstract
L-aspartate-α-decarboxylase (ADC) is a critical regulatory enzyme in the pantothenate biosynthetic pathway and belongs to a small class of self-cleaving and pyruvoyl-dependent amino acid decarboxylases. The expression level of ADC in Mycobacterium tuberculosis (Mtb) was confirmed by cDNA analysis, immunoblotting with an anti-ADC polyclonal antibody using whole cell lysate and immunoelectron microscopy. The recombinant ADC proenzyme from Mycobacterium tuberculosis (MtbADC) was overexpressed in E. coli and the protein structure was determined at 2.99 Å resolution. The proteins fold into the double-ψ β-barrel structure. The subunits of the two tetramers (there are eight ADC molecules in the asymmetric unit) form pseudo four-fold rotational symmetry, similar to the E. coli ADC proenzyme structure. As pantothenate is synthesized in microorganisms, plants, and fungi but not in animals, structure elucidation of Mtb ADC is of substantial interest for structure-based drug development. © 2006 Wiley-Liss, Inc.
Keywords
ADC, Crystal structure, Drug target, L-aspartate-α- decarboxylase, Mycobacterium tuberculosis, panD gene
Source Title
Proteins: Structure, Function and Genetics
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Series/Report No.
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Date
2006-12-01
DOI
10.1002/prot.21126
Type
Article