4hej

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:4hej.png|left|200px]]
+
==Discovery of Selective and Potent Inhibitors of Gram-positive Bacterial Thymidylate Kinase (TMK): Compund 16==
 +
<StructureSection load='4hej' size='340' side='right' caption='[[4hej]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[4hej]] is a 2 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HEJ FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gsy|4gsy]], [[4hdc|4hdc]]</td></tr>
 +
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SA0440, tmk ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158879 Staphylococcus aureus subsp. aureus N315])</td></tr>
 +
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] </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=4hej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hej OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hej RCSB], [http://www.ebi.ac.uk/pdbsum/4hej PDBsum]</span></td></tr>
 +
</table>
 +
<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.
-
{{STRUCTURE_4hej| PDB=4hej | SCENE= }}
+
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>
-
===Discovery of Selective and Potent Inhibitors of Gram-positive Bacterial Thymidylate Kinase (TMK): Compund 16===
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
-
{{ABSTRACT_PUBMED_23043329}}
+
==See Also==
-
 
+
*[[Thymidylate kinase|Thymidylate kinase]]
-
==About this Structure==
+
== References ==
-
[[4hej]] is a 2 chain structure with sequence from [http://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].
+
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Staphylococcus aureus subsp. aureus n315]]
[[Category: Staphylococcus aureus subsp. aureus n315]]
[[Category: DTMP kinase]]
[[Category: DTMP kinase]]
-
[[Category: Breen, J.]]
+
[[Category: Breen, J]]
-
[[Category: Duffy, J.]]
+
[[Category: Duffy, J]]
-
[[Category: Dumas, J.]]
+
[[Category: Dumas, J]]
-
[[Category: Geng, B.]]
+
[[Category: Geng, B]]
-
[[Category: Gowers, I.]]
+
[[Category: Gowers, I]]
-
[[Category: Green, O.]]
+
[[Category: Green, O]]
-
[[Category: Guler, S.]]
+
[[Category: Guler, S]]
-
[[Category: Hentemann, M.]]
+
[[Category: Hentemann, M]]
-
[[Category: Hernandez-Juan, F.]]
+
[[Category: Hernandez-Juan, F]]
-
[[Category: Joseph-McCarthy, D.]]
+
[[Category: Joseph-McCarthy, D]]
-
[[Category: Kawatkar, S.]]
+
[[Category: Kawatkar, S]]
-
[[Category: Larsen, N.]]
+
[[Category: Larsen, N]]
-
[[Category: Lazari, O.]]
+
[[Category: Lazari, O]]
-
[[Category: Loch, J.]]
+
[[Category: Loch, J]]
-
[[Category: Macritchie, J.]]
+
[[Category: Macritchie, J]]
-
[[Category: Martinez-Botella, G.]]
+
[[Category: Martinez-Botella, G]]
[[Category: Antibacterial]]
[[Category: Antibacterial]]
[[Category: Dna repair]]
[[Category: Dna repair]]

Revision as of 09:48, 10 December 2014

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

4hej, resolution 2.00Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4hej"
Personal tools