6kgs

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of Penicillin binding protein 3 (PBP3) from Mycobacterium tuerculosis, complexed with meropenem

Structural highlights

6kgs is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.309Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PBPB_MYCTU Synthesis of cross-linked peptidoglycan from the lipid intermediates.^[1]

Publication Abstract from PubMed

Because of beta-lactamase-mediated resistance, beta-lactam antibiotics were long considered ineffective drugs for tuberculosis (TB) treatment. However, some beta-lactams, including meropenem and faropenem, are being re-evaluated in patients infected with TB. Penicillin-binding protein (PBP) 3, or ftsI, is an essential transpeptidase in Mycobacterium tuberculosis (Mtb) required for cell division, and thus it is an important drug target. Structures of apo MtbPBP3 and of complexes with five beta-lactams, including meropenem and faropenem, reveal how they cause inactivation via formation of hydrolytically stable acyl-enzyme complexes. The structures reveal unique features of the antibiotic interactions, both in terms of differences in their binding to MtbPBP3 and in comparison with structures of other PBPs and serine beta-lactamases, including the tautomerization status of the carbapenem-derived acyl-enzyme complexes. The results suggest that rather than hoping PBP inhibitors developed for other infections will work against TB, work should focus on developing PBP inhibitors specialized for treating TB. SIGNIFICANCE STATEMENT: The structures of Mycobacterium tuberculosis penicillin-binding protein 3, an essential protein in M. tuberculosis, in complex with a number of widely used beta-lactam antibiotics (e.g., meropenem, aztreonam, and amoxicillin) were solved. These data provide new insights for next-generation rational approaches to design tuberculosis (TB)-specific beta-lactam or nonlactam antibiotics. This manuscript is a seminal article in the field of anti-TB drug discovery and suitable for the broad readership.

Structures of Mycobacterium tuberculosis Penicillin-Binding Protein 3 in Complex with Five beta-Lactam Antibiotics Reveal Mechanism of Inactivation.,Lu Z, Wang H, Zhang A, Liu X, Zhou W, Yang C, Guddat L, Yang H, Schofield CJ, Rao Z Mol Pharmacol. 2020 Apr;97(4):287-294. doi: 10.1124/mol.119.118042. Epub 2020 Feb, 21. PMID:32086254^[2]

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

References

↑ Mukherjee P, Sureka K, Datta P, Hossain T, Barik S, Das KP, Kundu M, Basu J. Novel role of Wag31 in protection of mycobacteria under oxidative stress. Mol Microbiol. 2009 Jul;73(1):103-19. doi: 10.1111/j.1365-2958.2009.06750.x. Epub, 2009 Jun 1. PMID:19496931 doi:http://dx.doi.org/10.1111/j.1365-2958.2009.06750.x
↑ Lu Z, Wang H, Zhang A, Liu X, Zhou W, Yang C, Guddat L, Yang H, Schofield CJ, Rao Z. Structures of Mycobacterium tuberculosis Penicillin-Binding Protein 3 in Complex with Five beta-Lactam Antibiotics Reveal Mechanism of Inactivation. Mol Pharmacol. 2020 Apr;97(4):287-294. doi: 10.1124/mol.119.118042. Epub 2020 Feb, 21. PMID:32086254 doi:http://dx.doi.org/10.1124/mol.119.118042

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/6kgs"

@@ Line 3: / Line 3: @@
 <StructureSection load='6kgs' size='340' side='right'caption='[[6kgs]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6kgs]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KGS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KGS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6kgs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KGS FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=MER:(4R,5S)-3-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-5-[(2S,3R)-3-HYDROXY-1-OXOBUTAN-2-YL]-4-METHYL-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>MER</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.309&#8491;</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=6kgs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kgs OCA], [http://pdbe.org/6kgs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kgs RCSB], [http://www.ebi.ac.uk/pdbsum/6kgs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kgs ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=MER:(4R,5S)-3-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-5-[(2S,3R)-3-HYDROXY-1-OXOBUTAN-2-YL]-4-METHYL-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>MER</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=6kgs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kgs OCA], [https://pdbe.org/6kgs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kgs RCSB], [https://www.ebi.ac.uk/pdbsum/6kgs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kgs ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PBPB_MYCTU PBPB_MYCTU]] Synthesis of cross-linked peptidoglycan from the lipid intermediates.<ref>PMID:19496931</ref>
+[https://www.uniprot.org/uniprot/PBPB_MYCTU PBPB_MYCTU] Synthesis of cross-linked peptidoglycan from the lipid intermediates.<ref>PMID:19496931</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 6kgs" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]]
 == References ==
 <references/>
@@ Line 23: / Line 27: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Guddat, L]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Liu, X]]
+[[Category: Guddat L]]
-[[Category: Lu, Z K]]
+[[Category: Liu X]]
-[[Category: Rao, Z H]]
+[[Category: Lu ZK]]
-[[Category: Yang, H T]]
+[[Category: Rao ZH]]
-[[Category: Zhang, A L]]
+[[Category: Yang HT]]
-[[Category: Meropenem]]
+[[Category: Zhang AL]]
-[[Category: Mycobacterium tuberculosis]]
-[[Category: Native form]]
-[[Category: Penicillin-binding protein]]
-[[Category: Transferase]]

6kgs

From Proteopedia

Current revision

Crystal structure of Penicillin binding protein 3 (PBP3) from Mycobacterium tuerculosis, complexed with meropenem

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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