6jvu: Difference between revisions
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==Crystal structure of Klebsiella pneumoniae CysE in complex with L-cysteine== | |||
<StructureSection load='6jvu' size='340' side='right'caption='[[6jvu]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6jvu]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae_MGH_78578 Klebsiella pneumoniae MGH 78578]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JVU FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=6jvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jvu OCA], [https://pdbe.org/6jvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jvu RCSB], [https://www.ebi.ac.uk/pdbsum/6jvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jvu ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A6TFK2_KLEP7 A6TFK2_KLEP7] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The emergence and spread of multidrug-resistant strains of Klebsiella pneumoniae is a major concern that necessitates the development of unique therapeutics. The essential requirement of serine acetyltransferase (SAT/CysE) for survival of several human pathogens makes it a very promising target for inhibitor designing and drug discovery. In this study, as an initial step to structure-based drug discovery, CysE from K. pneumonia was structurally and biochemically characterized. Subsequently, blind docking of selected natural products into the X-ray crystallography determined 3D structure of the target was carried out. Experimental validation of the inhibitory potential of the top-scorers established quercetin as an uncompetitive inhibitor of Kpn CysE. Molecular dynamics simulations carried out to elucidate the binding mode of quercetin reveal that this small molecule binds at the trimer-trimer interface of hexameric CysE, a site physically distinct from the active site of the enzyme. Detailed analysis of conformational differences incurred in Kpn CysE structure on binding to quercetin provides mechanistic understanding of allosteric modulation. Binding of quercetin to CysE leads to conformation changes in the active site loops and proximal loops that affect its internal dynamics and consequently its affinity for substrate/co-factor binding, justifying the reduced enzyme activity. | |||
Allosteric inhibition and kinetic characterization of Klebsiella pneumoniae CysE: An emerging drug target.,Verma D, Gupta S, Saxena R, Kaur P, R R, Srivastava S, Gupta V Int J Biol Macromol. 2019 Nov 18. pii: S0141-8130(19)36577-8. doi:, 10.1016/j.ijbiomac.2019.10.170. PMID:31751684<ref>PMID:31751684</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Gupta | <div class="pdbe-citations 6jvu" style="background-color:#fffaf0;"></div> | ||
[[Category: Verma | |||
==See Also== | |||
*[[Serine acetyltransferase|Serine acetyltransferase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Klebsiella pneumoniae MGH 78578]] | |||
[[Category: Large Structures]] | |||
[[Category: Gupta V]] | |||
[[Category: Verma D]] | |||
Latest revision as of 13:20, 22 November 2023
Crystal structure of Klebsiella pneumoniae CysE in complex with L-cysteineCrystal structure of Klebsiella pneumoniae CysE in complex with L-cysteine
Structural highlights
FunctionPublication Abstract from PubMedThe emergence and spread of multidrug-resistant strains of Klebsiella pneumoniae is a major concern that necessitates the development of unique therapeutics. The essential requirement of serine acetyltransferase (SAT/CysE) for survival of several human pathogens makes it a very promising target for inhibitor designing and drug discovery. In this study, as an initial step to structure-based drug discovery, CysE from K. pneumonia was structurally and biochemically characterized. Subsequently, blind docking of selected natural products into the X-ray crystallography determined 3D structure of the target was carried out. Experimental validation of the inhibitory potential of the top-scorers established quercetin as an uncompetitive inhibitor of Kpn CysE. Molecular dynamics simulations carried out to elucidate the binding mode of quercetin reveal that this small molecule binds at the trimer-trimer interface of hexameric CysE, a site physically distinct from the active site of the enzyme. Detailed analysis of conformational differences incurred in Kpn CysE structure on binding to quercetin provides mechanistic understanding of allosteric modulation. Binding of quercetin to CysE leads to conformation changes in the active site loops and proximal loops that affect its internal dynamics and consequently its affinity for substrate/co-factor binding, justifying the reduced enzyme activity. Allosteric inhibition and kinetic characterization of Klebsiella pneumoniae CysE: An emerging drug target.,Verma D, Gupta S, Saxena R, Kaur P, R R, Srivastava S, Gupta V Int J Biol Macromol. 2019 Nov 18. pii: S0141-8130(19)36577-8. doi:, 10.1016/j.ijbiomac.2019.10.170. PMID:31751684[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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