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5ah4

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Revision as of 04:59, 25 May 2023

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

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.
Ligands:	, , , , , ,
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^[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 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 <StructureSection load='5ah4' size='340' side='right'caption='[[5ah4]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ah4]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_smegmatis"_trevisan_1889 "bacillus smegmatis" trevisan 1889]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AH4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AH4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ah4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis Mycolicibacterium smegmatis] and [https://en.wikipedia.org/wiki/Streptomyces_muensis Streptomyces muensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AH4 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MLU:N-METHYL-D-LEUCINE'>MLU</scene>, <scene name='pdbligand=MP8:(4R)-4-METHYL-L-PROLINE'>MP8</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NZC:N-METHYLIDENE-L-THREONINE'>NZC</scene>, <scene name='pdbligand=PH6:(4S)-4-CYCLOHEXYL-L-PROLINE'>PH6</scene></td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MLU:N-METHYL-D-LEUCINE'>MLU</scene>, <scene name='pdbligand=MP8:(4R)-4-METHYL-L-PROLINE'>MP8</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=NZC:N-METHYLIDENE-L-THREONINE'>NZC</scene>, <scene name='pdbligand=PH6:(4S)-4-CYCLOHEXYL-L-PROLINE'>PH6</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ah4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ah4 OCA], [https://pdbe.org/5ah4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ah4 RCSB], [https://www.ebi.ac.uk/pdbsum/5ah4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ah4 ProSAT]</span></td></tr>
-<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://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 ==
-[[http://www.uniprot.org/uniprot/A0QND6_MYCS2 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]
+[https://www.uniprot.org/uniprot/DPO3B_MYCS2 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]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 20: @@
 ==See Also==
-*[[DNA polymerase|DNA polymerase]]
+*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Bacillus smegmatis trevisan 1889]]
-[[Category: DNA-directed DNA polymerase]]
 [[Category: Large Structures]]
-[[Category: Heinz, D W]]
+[[Category: Mycolicibacterium smegmatis]]
-[[Category: Kling, A]]
+[[Category: Streptomyces muensis]]
-[[Category: Lukat, P]]
+[[Category: Heinz DW]]
-[[Category: Mueller, R]]
+[[Category: Kling A]]
-[[Category: Dna polymerase]]
+[[Category: Lukat P]]
-[[Category: Dnan]]
+[[Category: Mueller R]]
-[[Category: Transferase-antibiotic complex]]
-[[Category: Tuberculosis]]

5ah4

From Proteopedia

Revision as of 04:59, 25 May 2023

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

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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