title: Crystal structures of Mycobacterium tuberculosis RecA and its complex with ADP-AlF(4): implications for decreased ATPase activity and molecular aggregation.
abstract: Sequencing of the complete genome of Mycobacterium tuberculosis, combined with the rapidly increasing need to improve tuberculosis management through better drugs and vaccines, has initiated extensive research on several key proteins from the pathogen. RecA, a ubiquitous multifunctional protein, is a key component of the processes of homologous genetic recombination and DNA repair. Structural knowledge of MtRecA is imperative for a full understanding of both these activities and any ensuing application. The crystal structure of MtRecA, presented here, has six molecules in the unit cell forming a 6(1) helical filament with a deep groove capable of binding DNA. The observed weakening in the higher order aggregation of filaments into bundles may have implications for recombination in mycobacteria. The structure of the complex reveals the atomic interactions of ADP-AlF(4), an ATP analogue, with the P-loop-containing binding pocket. The structures explain reduced levels of interactions of MtRecA with ATP, despite sharing the same fold, topology and high sequence similarity with EcRecA. The formation of a helical filament with a deep groove appears to be an inherent property of MtRecA. The histidine in loop L1 appears to be positioned appropriately for DNA interaction.
authors: Molecular Biophysics Unit, Department of Biochemistry and Bioinformatics Centre, Indian Institute of Science, Bangalore 560 012, India.
authors: S
authors: S
authors: Datta
authors: M M
authors: MM
authors: Prabu
authors: M B
authors: MB
authors: Vaze
authors: N
authors: N
authors: Ganesh
authors: N R
authors: NR
authors: Chandra
authors: K
authors: K
authors: Muniyappa
authors: M
authors: M
authors: Vijayan
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D017607:Aluminum Compounds / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D004260:DNA Repair; D005459:Fluorides / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism; D006860:Hydrogen Bonding; D006868:Hydrolysis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D011938:Rec A Recombinases / Q000737:chemistry* / Q000378:metabolism*; D011995:Recombination, Genetic; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
chemical_list: D017607:Aluminum Compounds; D001704:Biopolymers; D006639:Histidine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011938:Rec A Recombinases; D000251:Adenosine Triphosphatases; D005459:Fluorides; C032311:aluminum fluoride