TAILIEUCHUNG - Báo cáo khoa học: Hexameric ring structure of the N-terminal domain of Mycobacterium tuberculosis DnaB helicase

Hexameric DnaB helicase unwinds the DNA double helix during replica-tion of genetic material in bacteria. DnaB is an essential bacterial protein; therefore, it is an important potential target for antibacterial drug disco-very. We report a crystal structure of the N-terminal region of DnaB from the pathogen Mycobacterium tuberculosis(MtDnaBn), determined at A˚ resolution. | ễFEBS Journal Hexameric ring structure of the N-terminal domain of Mycobacterium tuberculosis DnaB helicase Tapan Biswas and Oleg V. Tsodikov Department of MedicinalChemistry College of Pharmacy University of Michigan Ann Arbor MI USA Keywords crystal structure DnaB helicase primase replication tuberculosis Correspondence O. V. Tsodikov Department of Medicinal Chemistry College of Pharmacy University of Michigan Ann Arbor MI 48109-1065 USA Fax 1 734 647 8430 Tel 1 734 936 2676 E-mail olegt@ Received 19 March 2008 revised 8 April 2008 accepted 11 April 2008 Hexameric DnaB helicase unwinds the DNA double helix during replication of genetic material in bacteria. DnaB is an essential bacterial protein therefore it is an important potential target for antibacterial drug discovery. We report a crystal structure of the N-terminal region of DnaB from the pathogen Mycobacterium tuberculosis MtDnaBn determined at A resolution. This structure provides atomic resolution details of formation of the hexameric ring of DnaB by two distinct interfaces. An extensive hydrophobic interface stabilizes a dimer of MtDnaBn by forming a four-helix bundle. The other less extensive interface is formed between the dimers connecting three of them into a hexameric ring. On the basis of crystal packing interactions between MtDnaBn rings we suggest a model of a helicase-primase complex that explains previously observed effects of DnaB mutations on DNA priming. doi The DnaB gene encoding DnaB helicase was originally identified in a region of the bacterial genome mutations in which caused a defect in DNA replication at elevated temperatures in vivo 1 . DnaB is an ATP-dependent helicase that unwinds parental duplex DNA during replication 2-5 thereby allowing the two strands to be copied. A hexamer of DnaB encircles the lagging strand and moves on it in the 5 fi 3 direction thereby splitting the two complementary DNA strands 6 . A hexameric DnaB helicase

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