View source for 4olg


==Crystal structure of AmpC beta-lactamase in complex with covalently bound N-formyl 7-aminocephalosporanic acid==
<StructureSection load='4olg' size='340' side='right'caption='[[4olg]], [[Resolution|resolution]] 1.71&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4olg]] 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=4OLG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OLG 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]] 1.71&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2TV:(2R,5Z)-5-[(ACETYLOXY)METHYLIDENE]-2-[(1R)-1-(FORMYLAMINO)-2-OXOETHYL]-5,6-DIHYDRO-2H-1,3-THIAZINE-4-CARBOXYLIC+ACID'>2TV</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=4olg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4olg OCA], [https://pdbe.org/4olg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4olg RCSB], [https://www.ebi.ac.uk/pdbsum/4olg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4olg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Predicting substrates for enzymes of unknown function is a major postgenomic challenge. Substrate discovery, like inhibitor discovery, is constrained by our ability to explore chemotypes; it would be expanded by orders of magnitude if reactive sites could be probed with fragments rather than fully elaborated substrates, as is done for inhibitor discovery. To explore the feasibility of this approach, substrates of six enzymes from three different superfamilies were deconstructed into 41 overlapping fragments that were tested for activity or binding. Surprisingly, even those fragments containing the key reactive group had little activity, and most fragments did not bind measurably, until they captured most of the substrate features. Removing a single atom from a recognized substrate could often reduce catalytic recognition by 6 log-orders. To explore recognition at atomic resolution, the structures of three fragment complexes of the beta-lactamase substrate cephalothin were determined by X-ray crystallography. Substrate discovery may be difficult to reduce to the fragment level, with implications for function discovery and for the tolerance of enzymes to metabolite promiscuity. Pragmatically, this study supports the development of libraries of fully elaborated metabolites as probes for enzyme function, which currently do not exist.

Substrate deconstruction and the nonadditivity of enzyme recognition.,Barelier S, Cummings JA, Rauwerdink AM, Hitchcock DS, Farelli JD, Almo SC, Raushel FM, Allen KN, Shoichet BK J Am Chem Soc. 2014 May 21;136(20):7374-82. doi: 10.1021/ja501354q. Epub 2014 May, 12. PMID:24791931<ref>PMID:24791931</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4olg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Barelier S]]
[[Category: Shoichet BK]]