2hds

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(New page: 200px<br /><applet load="2hds" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hds, resolution 1.160&Aring;" /> '''AmpC beta-lactamase...)
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[[Image:2hds.gif|left|200px]]<br /><applet load="2hds" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2hds, resolution 1.160&Aring;" />
 
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'''AmpC beta-lactamase in complex with 4-Methanesulfonylamino benzoic acid'''<br />
 
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==Overview==
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==AmpC beta-lactamase in complex with 4-Methanesulfonylamino benzoic acid==
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Fragment-based screens test multiple low-molecular weight molecules for, binding to a target. Fragments often bind with low affinities but, typically have better ligand efficiencies (DeltaG(bind)/heavy atom count), than traditional screening hits. This efficiency, combined with, accompanying atomic-resolution structures, has made fragments popular, starting points for drug discovery programs. Fragment-based design adopts, a constructive strategy: affinity is enhanced either by cycles of, functional-group addition or by joining two independent fragments, together. The final inhibitor is expected to adopt the same geometry as, the original fragment hit. Here we consider whether the inverse, deconstructive logic also applies--can one always parse a higher-affinity, inhibitor into fragments that recapitulate the binding geometry of the, larger molecule? Cocrystal structures of fragments deconstructed from a, known beta-lactamase inhibitor suggest that this is not always the case.
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<StructureSection load='2hds' size='340' side='right'caption='[[2hds]], [[Resolution|resolution]] 1.16&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2hds]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HDS FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.16&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4MB:4-[(METHYLSULFONYL)AMINO]BENZOIC+ACID'>4MB</scene>, <scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=PRD_900003:sucrose'>PRD_900003</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hds OCA], [https://pdbe.org/2hds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hds RCSB], [https://www.ebi.ac.uk/pdbsum/2hds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hds ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hd/2hds_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2hds ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Fragment-based screens test multiple low-molecular weight molecules for binding to a target. Fragments often bind with low affinities but typically have better ligand efficiencies (DeltaG(bind)/heavy atom count) than traditional screening hits. This efficiency, combined with accompanying atomic-resolution structures, has made fragments popular starting points for drug discovery programs. Fragment-based design adopts a constructive strategy: affinity is enhanced either by cycles of functional-group addition or by joining two independent fragments together. The final inhibitor is expected to adopt the same geometry as the original fragment hit. Here we consider whether the inverse, deconstructive logic also applies--can one always parse a higher-affinity inhibitor into fragments that recapitulate the binding geometry of the larger molecule? Cocrystal structures of fragments deconstructed from a known beta-lactamase inhibitor suggest that this is not always the case.
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==About this Structure==
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Deconstructing fragment-based inhibitor discovery.,Babaoglu K, Shoichet BK Nat Chem Biol. 2006 Dec;2(12):720-3. Epub 2006 Oct 29. PMID:17072304<ref>PMID:17072304</ref>
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2HDS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with SUC, PO4, NA and 4MB as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2HDS OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Deconstructing fragment-based inhibitor discovery., Babaoglu K, Shoichet BK, Nat Chem Biol. 2006 Dec;2(12):720-3. Epub 2006 Oct 29. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17072304 17072304]
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</div>
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[[Category: Beta-lactamase]]
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<div class="pdbe-citations 2hds" style="background-color:#fffaf0;"></div>
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[[Category: Escherichia coli]]
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[[Category: Single protein]]
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[[Category: Babaoglu, K.]]
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[[Category: Shoichet, B.K.]]
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[[Category: 4MB]]
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[[Category: NA]]
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[[Category: PO4]]
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[[Category: SUC]]
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[[Category: ampc beta-lactamase fragment-based drug design]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 11:41:45 2007''
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==See Also==
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*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Escherichia coli K-12]]
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[[Category: Large Structures]]
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[[Category: Babaoglu K]]
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[[Category: Shoichet BK]]

Current revision

AmpC beta-lactamase in complex with 4-Methanesulfonylamino benzoic acid

PDB ID 2hds

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