2am2: Difference between revisions
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== | ==sp protein ligand 2== | ||
<StructureSection load='2am2' size='340' side='right'caption='[[2am2]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2am2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_R6 Streptococcus pneumoniae R6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AM2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AM2 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=2LG:2-CHLORO-N-(3-CYANO-5,6-DIHYDRO-4H-CYCLOPENTA[B]THIOPHEN-2-YL)-5-DIETHYLSULFAMOYL-BENZAMIDE'>2LG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=2am2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2am2 OCA], [https://pdbe.org/2am2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2am2 RCSB], [https://www.ebi.ac.uk/pdbsum/2am2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2am2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8DNV6_STRR6 Q8DNV6_STRR6] Involved in cell wall formation. Catalyzes the final step in the synthesis of UDP-N-acetylmuramoyl-pentapeptide, the precursor of murein (By similarity).[RuleBase:RU004136] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/am/2am2_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2am2 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In a broad genomics analysis to find novel protein targets for antibiotic discovery, MurF was identified as an essential gene product for Streptococcus pneumonia that catalyzes a critical reaction in the biosynthesis of the peptidoglycan in the formation of the cell wall. Lacking close relatives in mammalian biology, MurF presents attractive characteristics as a potential drug target. Initial screening of the Abbott small-molecule compound collection identified several compounds for further validation as pharmaceutical leads. Here we report the integrated efforts of NMR and X-ray crystallography, which reveal the multidomain structure of a MurF-inhibitor complex in a compact conformation that differs dramatically from related structures. The lead molecule is bound in the substrate-binding region and induces domain closure, suggestive of the domain arrangement for the as yet unobserved transition state conformation for MurF enzymes. The results form a basis for directed optimization of the compound lead by structure-based design to explore the suitability of MurF as a pharmaceutical target. | In a broad genomics analysis to find novel protein targets for antibiotic discovery, MurF was identified as an essential gene product for Streptococcus pneumonia that catalyzes a critical reaction in the biosynthesis of the peptidoglycan in the formation of the cell wall. Lacking close relatives in mammalian biology, MurF presents attractive characteristics as a potential drug target. Initial screening of the Abbott small-molecule compound collection identified several compounds for further validation as pharmaceutical leads. Here we report the integrated efforts of NMR and X-ray crystallography, which reveal the multidomain structure of a MurF-inhibitor complex in a compact conformation that differs dramatically from related structures. The lead molecule is bound in the substrate-binding region and induces domain closure, suggestive of the domain arrangement for the as yet unobserved transition state conformation for MurF enzymes. The results form a basis for directed optimization of the compound lead by structure-based design to explore the suitability of MurF as a pharmaceutical target. | ||
Structure of MurF from Streptococcus pneumoniae co-crystallized with a small molecule inhibitor exhibits interdomain closure.,Longenecker KL, Stamper GF, Hajduk PJ, Fry EH, Jakob CG, Harlan JE, Edalji R, Bartley DM, Walter KA, Solomon LR, Holzman TF, Gu YG, Lerner CG, Beutel BA, Stoll VS Protein Sci. 2005 Dec;14(12):3039-47. PMID:16322581<ref>PMID:16322581</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2am2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Mur ligase|Mur ligase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Streptococcus pneumoniae R6]] | |||
[[Category: Bartley DM]] | |||
[[Category: Edalji R]] | |||
[[Category: Fry EH]] | |||
[[Category: Hajduk PJ]] | |||
[[Category: Harlan JE]] | |||
[[Category: Jakob CG]] | |||
[[Category: Longenecker KL]] | |||
[[Category: Solomon LR]] | |||
[[Category: Stamper GF]] | |||
[[Category: Walter KA]] | |||
Latest revision as of 10:49, 30 October 2024
sp protein ligand 2sp protein ligand 2
Structural highlights
FunctionQ8DNV6_STRR6 Involved in cell wall formation. Catalyzes the final step in the synthesis of UDP-N-acetylmuramoyl-pentapeptide, the precursor of murein (By similarity).[RuleBase:RU004136] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedIn a broad genomics analysis to find novel protein targets for antibiotic discovery, MurF was identified as an essential gene product for Streptococcus pneumonia that catalyzes a critical reaction in the biosynthesis of the peptidoglycan in the formation of the cell wall. Lacking close relatives in mammalian biology, MurF presents attractive characteristics as a potential drug target. Initial screening of the Abbott small-molecule compound collection identified several compounds for further validation as pharmaceutical leads. Here we report the integrated efforts of NMR and X-ray crystallography, which reveal the multidomain structure of a MurF-inhibitor complex in a compact conformation that differs dramatically from related structures. The lead molecule is bound in the substrate-binding region and induces domain closure, suggestive of the domain arrangement for the as yet unobserved transition state conformation for MurF enzymes. The results form a basis for directed optimization of the compound lead by structure-based design to explore the suitability of MurF as a pharmaceutical target. Structure of MurF from Streptococcus pneumoniae co-crystallized with a small molecule inhibitor exhibits interdomain closure.,Longenecker KL, Stamper GF, Hajduk PJ, Fry EH, Jakob CG, Harlan JE, Edalji R, Bartley DM, Walter KA, Solomon LR, Holzman TF, Gu YG, Lerner CG, Beutel BA, Stoll VS Protein Sci. 2005 Dec;14(12):3039-47. PMID:16322581[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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