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5ah4

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Revision as of 17:04, 22 March 2017

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

Structural highlights

5ah4 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:	, , , , ,
Related:	5agu, 5agv, 5ah2
Activity:	DNA-directed DNA polymerase, with EC number 2.7.7.7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[A0QND6_MYCS2] DNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. This DNA polymerase also exhibits 3' to 5' exonuclease activity. The beta chain is required for initiation of replication once it is clamped onto DNA, it slides freely (bidirectional and ATP-independent) along duplex DNA.[PIRNR:PIRNR000804]

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. Antibiotics. Targeting DnaN for tuberculosis therapy using novel griselimycins. Science. 2015 Jun 5;348(6239):1106-12. doi: 10.1126/science.aaa4690. PMID:26045430 doi:http://dx.doi.org/10.1126/science.aaa4690

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ah4"

@@ Line 1: / Line 1: @@
 ==The sliding clamp of Mycobacterium smegmatis in complex with a natural product.==
 <StructureSection load='5ah4' size='340' side='right' caption='[[5ah4]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5agu|5agu]], [[5agv|5agv]], [[5ah2|5ah2]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ah4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ah4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5ah4 RCSB], [http://www.ebi.ac.uk/pdbsum/5ah4 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ah4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ah4 OCA], [http://pdbe.org/5ah4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ah4 RCSB], [http://www.ebi.ac.uk/pdbsum/5ah4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ah4 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 5ah4" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

5ah4

From Proteopedia

Revision as of 17:04, 22 March 2017

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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