3uc1
Mycobacterium tuberculosis gyrase type IIA topoisomerase C-terminal domainMycobacterium tuberculosis gyrase type IIA topoisomerase C-terminal domain
Structural highlights
Publication Abstract from PubMedDNA topoisomerases are essential enzymes that can overwind, underwind, and disentangle double-helical DNA segments to maintain the topological state of chromosomes. Nearly all bacteria utilize a unique type II topoisomerase, gyrase, which actively adds negative supercoils to chromosomes using an ATP-dependent DNA strand passage mechanism; however, the specific activities of these enzymes can vary markedly from species to species. E. coli gyrase is known to favor supercoiling over decatenation (1), whereas the opposite has been reported for Mycobacterium tuberculosis (Mtb) gyrase (2). Here, we set out to understand the molecular basis for these differences using structural and biochemical approaches. Contrary to expectations based on phylogenetic inferences (3), we find that the dedicated DNA wrapping domains (the CTDs) of both gyrases are highly similar, both architecturally and in their ability to introduce writhe into DNA. However, the Mtb enzyme lacks a C-terminal control element recently uncovered in E. coli gyrase (see accompanying paper), and turns over ATP at a much slower rate. Together, these findings demonstrate that CTD shape is not the sole regulatory determinant of gyrase activity, and instead indicate that an inability to tightly couple DNA wrapping to ATP turnover is why Mtb gyrase cannot supercoil DNA to the same extent as its gamma-proteobacterial counterpart. Our observations demonstrate that gyrase has been modified in multiple ways throughout evolution to fine-tune its specific catalytic properties. Mechanisms For Defining Supercoiling Setpoint By DNA Gyrase Orthologs II. The shape of the GyrA CTD is not a sole determinant for controlling supercoiling efficiency.,Tretter EM, Berger JM J Biol Chem. 2012 Mar 28. PMID:22457352[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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