5d5h

Crystal structure of Mycobacterium tuberculosis Topoisomerase I

spinqualitylabelsall models 5d5h, resolution 2.52Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5d5h is a 1 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, GOL, SO4 Gene: topA, Rv3646c, MTCY15C10.06 (MYCTU) Activity: DNA topoisomerase, with EC number 5.99.1.2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [TOP1_MYCTU] Releases the supercoiling and torsional tension of DNA, which is introduced during the DNA replication and transcription, by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone.[HAMAP-Rule:MF_00952] The C-terminus (residues 622-934) inhibits RNA cleavage by MazF4. Publication Abstract from PubMed The DNA topoisomerase I enzyme of Mycobacterium tuberculosis (MtTOP1) is essential for the viability of the organism and survival in a murine model. This topoisomerase is being pursued as a novel target for the discovery of new therapeutic agents for the treatment of drug-resistant tuberculosis. In this study, we succeeded in obtaining a structure of MtTOP1 by first predicting that the C-terminal region of MtTOP1 contains four repeated domains that do not involve the Zn-binding tetracysteine motifs seen in the C-terminal domains of Escherichiacoli topoisomerase I. A construct (amino acids A2-T704), MtTOP1-704t, that includes the N-terminal domains (D1-D4) and the first predicted C-terminal domain (D5) of MtTOP1 was expressed and found to retain DNA cleavage-religation activity and catalyze single-stranded DNA catenation. MtTOP1-704t was crystallized, and a structure of 2.52A resolution limit was obtained. The structure of the MtTOP1 N-terminal domains has features that have not been observed in other previously available bacterial topoisomerase I crystal structures. The first C-terminal domain D5 forms a novel protein fold of a four-stranded antiparallel beta-sheet stabilized by a crossing-over alpha-helix. Since there is only one type IA topoisomerase present in Mycobacteriaceae and related Actinobacteria, this subfamily of type IA topoisomerase may be required for multiple functions in DNA replication, transcription, recombination, and repair. The unique structural features observed for MtTOP1 may allow these topoisomerase I enzymes to carry out physiological functions associated with topoisomerase III enzyme in other bacteria. Insights from the Structure of Mycobacterium tuberculosis Topoisomerase I with a Novel Protein Fold.,Tan K, Cao N, Cheng B, Joachimiak A, Tse-Dinh YC J Mol Biol. 2015 Dec 3. pii: S0022-2836(15)00686-5. doi:, 10.1016/j.jmb.2015.11.024. PMID:26655023 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Topoisomerase

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