4hej: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4hej]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_N315 Staphylococcus aureus subsp. aureus N315]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HEJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HEJ FirstGlance]. <br>
<table><tr><td colspan='2'>[[4hej]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_N315 Staphylococcus aureus subsp. aureus N315]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HEJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HEJ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=14D:5-METHYL-1-[(3S)-1-{3-[3-(TRIFLUOROMETHYL)PHENOXY]BENZYL}PIPERIDIN-3-YL]PYRIMIDINE-2,4(1H,3H)-DIONE'>14D</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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=14D:5-METHYL-1-[(3S)-1-{3-[3-(TRIFLUOROMETHYL)PHENOXY]BENZYL}PIPERIDIN-3-YL]PYRIMIDINE-2,4(1H,3H)-DIONE'>14D</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=4hej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hej OCA], [https://pdbe.org/4hej PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hej RCSB], [https://www.ebi.ac.uk/pdbsum/4hej PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hej ProSAT]</span></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=4hej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hej OCA], [https://pdbe.org/4hej PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hej RCSB], [https://www.ebi.ac.uk/pdbsum/4hej PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hej ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/KTHY_STAAN KTHY_STAAN] Phosphorylation of dTMP to form dTDP in both de novo and salvage pathways of dTTP synthesis.[HAMAP-Rule:MF_00165]
[https://www.uniprot.org/uniprot/KTHY_STAAN KTHY_STAAN] Phosphorylation of dTMP to form dTDP in both de novo and salvage pathways of dTTP synthesis.[HAMAP-Rule:MF_00165]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Thymidylate kinase (TMK) is an essential enzyme in bacterial DNA synthesis. The deoxythymidine monophosphate (dTMP) substrate binding pocket was targeted in a rational-design, structure-supported effort yielding a unique series of antibacterial agents showing a novel, induced-fit binding mode. Lead optimization, aided by x-ray crystallography, led to picomolar inhibitors of both Streptococcus pneumoniae and Staphylococcus aureus TMK. MICs &lt;1 ug/mL were achieved against methicillin-resistant S. aureus (MRSA), S. pneumoniae, and vancomycin-resistant Enterococcus (VRE). Log D adjustments yielded single diastereomers 14 (TK-666) and 46, showing a broad antibacterial spectrum against Gram-positive bacteria and excellent selectivity against the human thymidylate kinase ortholog.
Discovery of Selective and Potent Inhibitors of Gram-positive Bacterial Thymidylate Kinase (TMK).,Martinez-Botella G, Breen JN, Duffy JE, Dumas J, Geng B, Gowers IK, Green OM, Guler S, Hentemann MF, Hernandez-Juan FA, Joseph-McCarthy D, Kawatkar SP, Larsen NA, Lazari O, Loch JT, Macritchie JA, McKenzie AR, Newman JV, Olivier NB, Otterson LG, Owens AP, Read J, Sheppard DW, Keating TA J Med Chem. 2012 Oct 8. PMID:23043329<ref>PMID:23043329</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4hej" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]]
*[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Latest revision as of 14:40, 1 March 2024

Discovery of Selective and Potent Inhibitors of Gram-positive Bacterial Thymidylate Kinase (TMK): Compund 16Discovery of Selective and Potent Inhibitors of Gram-positive Bacterial Thymidylate Kinase (TMK): Compund 16

Structural highlights

4hej is a 2 chain structure with sequence from Staphylococcus aureus subsp. aureus N315. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KTHY_STAAN Phosphorylation of dTMP to form dTDP in both de novo and salvage pathways of dTTP synthesis.[HAMAP-Rule:MF_00165]

See Also

4hej, resolution 2.00Å

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