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Crystallographic and solution structure of the N‐terminal domain of the Rel protein from Mycobacterium tuberculosis
Author(s) -
Singal Bharti,
Balakrishna Asha Manikkoth,
Nartey Wilson,
Manimekalai Malathy Sony Subramanian,
Jeyakanthan Jeyaraman,
Grüber Gerhard
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12739
Subject(s) - guanosine , hydrolase , stringent response , mycobacterium tuberculosis , effector , chemistry , biology , protein structure , c terminus , mycobacterium smegmatis , biochemistry , enzyme , amino acid , gene , tuberculosis , escherichia coli , medicine , pathology
Modulation of intracellular guanosine 3′,5′‐bispyrophosphate ((p)ppGpp) level, the effector of the stringent response, is crucial for survival as well as optimal growth of prokaryotes and, thus, for bacterial pathogenesis and dormancy. In Mycobacterium tuberculosis ( Mtb ), (p)ppGpp synthesis and degradation are carried out by the bifunctional enzyme Mt Rel, which consists of 738 residues, including an N‐terminal hydrolase‐ and synthetase‐domain (N‐terminal domain or NTD ) and a C‐terminus with a ribosome‐binding site. Here, we present the first crystallographic structure of the enzymatically active Mt Rel NTD determined at 3.7 Å resolution. The structure provides insights into the residues of Mt Rel NTD responsible for nucleotide binding. Small‐angle X‐ray scattering experiments were performed to investigate the dimeric state of the Mt Rel NTD and possible substrate‐dependent structural alterations.