4xuz: Difference between revisions

Revision as of 17:53, 26 April 2023

Structure of CTX-M-15 bound to RPX-7009 at 1.5 A

Structural highlights

4xuz is a 1 chain structure with sequence from Klebsiella pneumoniae subsp. pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	4D6, CIT, CL, EDO
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

S5LVN3_KLEPN

Publication Abstract from PubMed

The increasing dissemination of carbapenemases in Gram-negative bacteria has threatened the clinical usefulness of the beta-lactam class of antimicrobials. A program was initiated to discover a new series of serine beta-lactamase inhibitors containing a boronic acid pharmacophore, with the goal of finding a potent inhibitor of serine carbapenemase enzymes that are currently compromising the utility of the carbapenem class of antibacterials. Potential lead structures were screened in silico by modeling into the active sites of key serine beta-lactamases. Promising candidate molecules were synthesized and evaluated in biochemical and whole-cell assays. Inhibitors were identified with potent inhibition of serine carbapenemases, particularly the Klebsiella pneumoniae carbapenemase (KPC), with no inhibition of mammalian serine proteases. Studies in vitro and in vivo show that RPX7009 (9f) is a broad-spectrum inhibitor, notably restoring the activity of carbapenems against KPC-producing strains. Combined with a carbapenem, 9f is a promising product for the treatment of multidrug resistant Gram-negative bacteria.

Discovery of a Cyclic Boronic Acid beta-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases.,Hecker SJ, Reddy KR, Totrov M, Hirst GC, Lomovskaya O, Griffith DC, King P, Tsivkovski R, Sun D, Sabet M, Tarazi Z, Clifton MC, Atkins K, Raymond A, Potts KT, Abendroth J, Boyer SH, Loutit JS, Morgan EE, Durso S, Dudley MN J Med Chem. 2015 Mar 17. PMID:25782055^[1]

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

References

↑ Hecker SJ, Reddy KR, Totrov M, Hirst GC, Lomovskaya O, Griffith DC, King P, Tsivkovski R, Sun D, Sabet M, Tarazi Z, Clifton MC, Atkins K, Raymond A, Potts KT, Abendroth J, Boyer SH, Loutit JS, Morgan EE, Durso S, Dudley MN. Discovery of a Cyclic Boronic Acid beta-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases. J Med Chem. 2015 Mar 17. PMID:25782055 doi:https://dx.doi.org/10.1021/acs.jmedchem.5b00127

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OCA

[1] Hecker SJ, Reddy KR, Totrov M, Hirst GC, Lomovskaya O, Griffith DC, King P, Tsivkovski R, Sun D, Sabet M, Tarazi Z, Clifton MC, Atkins K, Raymond A, Potts KT, Abendroth J, Boyer SH, Loutit JS, Morgan EE, Durso S, Dudley MN. Discovery of a Cyclic Boronic Acid beta-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases. J Med Chem. 2015 Mar 17. PMID:25782055 doi:https://dx.doi.org/10.1021/acs.jmedchem.5b00127

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='4xuz' size='340' side='right'caption='[[4xuz]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4xuz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Citrobacter_sp._43uckpc_blue2plate Citrobacter sp. 43uckpc_blue2plate]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XUZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XUZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4xuz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae_subsp._pneumoniae Klebsiella pneumoniae subsp. pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XUZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4D6:{(3R,6S)-2-HYDROXY-3-[(THIOPHEN-2-YLACETYL)AMINO]-1,2-OXABORINAN-6-YL}ACETIC+ACID'>4D6</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4D6:{(3R,6S)-2-HYDROXY-3-[(THIOPHEN-2-YLACETYL)AMINO]-1,2-OXABORINAN-6-YL}ACETIC+ACID'>4D6</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xux|4xux]]</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=4xuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xuz OCA], [https://pdbe.org/4xuz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xuz RCSB], [https://www.ebi.ac.uk/pdbsum/4xuz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xuz ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaCTX-M-15, KPNIH31_23215 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=72407 Citrobacter sp. 43UCKPC_BLUE2PLATE])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </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=4xuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xuz OCA], [http://pdbe.org/4xuz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xuz RCSB], [http://www.ebi.ac.uk/pdbsum/4xuz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xuz ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/S5LVN3_KLEPN S5LVN3_KLEPN]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Beta-lactamase]]
+[[Category: Klebsiella pneumoniae subsp. pneumoniae]]
-[[Category: Citrobacter sp. 43uckpc_blue2plate]]
 [[Category: Large Structures]]
-[[Category: Clifton, M C]]
+[[Category: Clifton MC]]
-[[Category: Gardberg, A]]
+[[Category: Gardberg A]]
-[[Category: Hydrolase-antibiotic complex]]

4xuz: Difference between revisions

Revision as of 17:53, 26 April 2023

Structure of CTX-M-15 bound to RPX-7009 at 1.5 A

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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