5ah4 | pdb_00005ah4

The sliding clamp of Mycobacterium smegmatis in complex with a natural product.

spinqualitylabelsall models 5ah4, resolution 2.31Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ah4 is a 4 chain structure with sequence from Mycolicibacterium smegmatis and Streptomyces muensis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.313Å Ligands: ACE, MLU, MP8, MVA, NA, NZC, PH6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DPO3B_MYCS2 Confers DNA tethering and processivity to DNA polymerases and other proteins. Acts as a clamp, forming a ring around DNA (a reaction catalyzed by the clamp-loading complex) which diffuses in an ATP-independent manner freely and bidirectionally along dsDNA. Initially characterized for its ability to contact the catalytic subunit of DNA polymerase III (Pol III), a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria; Pol III exhibits 3'-5' exonuclease proofreading activity. The beta chain is required for initiation of replication as well as for processivity of DNA replication.[UniProtKB:P0A988] Publication Abstract from PubMed The discovery of Streptomyces-produced streptomycin founded the age of tuberculosis therapy. Despite the subsequent development of a curative regimen for this disease, tuberculosis remains a worldwide problem, and the emergence of multidrug-resistant Mycobacterium tuberculosis has prioritized the need for new drugs. Here we show that new optimized derivatives from Streptomyces-derived griselimycin are highly active against M. tuberculosis, both in vitro and in vivo, by inhibiting the DNA polymerase sliding clamp DnaN. We discovered that resistance to griselimycins, occurring at very low frequency, is associated with amplification of a chromosomal segment containing dnaN, as well as the ori site. Our results demonstrate that griselimycins have high translational potential for tuberculosis treatment, validate DnaN as an antimicrobial target, and capture the process of antibiotic pressure-induced gene amplification. Antibiotics. Targeting DnaN for tuberculosis therapy using novel griselimycins.,Kling A, Lukat P, Almeida DV, Bauer A, Fontaine E, Sordello S, Zaburannyi N, Herrmann J, Wenzel SC, Konig C, Ammerman NC, Barrio MB, Borchers K, Bordon-Pallier F, Bronstrup M, Courtemanche G, Gerlitz M, Geslin M, Hammann P, Heinz DW, Hoffmann H, Klieber S, Kohlmann M, Kurz M, Lair C, Matter H, Nuermberger E, Tyagi S, Fraisse L, Grosset JH, Lagrange S, Muller R Science. 2015 Jun 5;348(6239):1106-12. doi: 10.1126/science.aaa4690. PMID:26045430 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA polymerase 3D structures

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