New paper in PNAS: a cloaked glutamate decarboxylase in Mycobacterium tuberculosis
Published:
Our paper “A cloaked glutamate decarboxylase sustains the GABA shunt in Mycobacterium tuberculosis” is out in Proceedings of the National Academy of Sciences.
Mycobacterium tuberculosis Rv2531c had long been annotated as a lysine/ornithine/arginine decarboxylase, a superfamily of more than 26,000 sequences. It isn’t one. Combining bioinformatics, microbiology, metabolomics and enzymology, we demonstrate that it is instead an L-glutamate decarboxylase that sustains carbon flux through the γ-aminobutyric acid (GABA) shunt in M. tuberculosis.
I contributed the creation and analysis of the sequence similarity network that placed Rv2531c in the context of its enzyme family, showing that the superfamily is composed of distinct forms with different domain organisations, and that Rv2531c belongs to a group in which no enzyme had been experimentally characterised.
A good reminder of how easily annotation bias propagates across homologous sequences, and of what network-based approaches can reveal when we look at a family as a whole rather than one sequence at a time.
Work led by H. Minh Thai and Luiz Pedro S. de Carvalho, with Debbie M. Hunt, Yugen Miyahara, Manisha Priya and Htin L. Aung.
Read the paper: 10.1073/pnas.2619778123