1erq: Difference between revisions

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-{{Seed}}
-[[Image:1erq.png|left|200px]]
-<!--
+==X-RAY CRYSTAL STRUCTURE OF TEM-1 BETA LACTAMASE IN COMPLEX WITH A DESIGNED BORONIC ACID INHIBITOR (1R)-1-ACETAMIDO-2-(3-CARBOXY-2-HYDROXYPHENYL)ETHYL BORONIC ACID==
-The line below this paragraph, containing "STRUCTURE_1erq", creates the "Structure Box" on the page.
+<StructureSection load='1erq' size='340' side='right'caption='[[1erq]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1erq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ERQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ERQ FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BJH:1(R)-1-ACETAMIDO-2-(3-CARBOXY-2-HYDROXYPHENYL)ETHYL+BORONIC+ACID'>BJH</scene></td></tr>
-{{STRUCTURE_1erq|  PDB=1erq  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1erq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1erq OCA], [https://pdbe.org/1erq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1erq RCSB], [https://www.ebi.ac.uk/pdbsum/1erq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1erq ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/BLAT_ECOLX BLAT_ECOLX] TEM-type are the most prevalent beta-lactamases in enterobacteria; they hydrolyze the beta-lactam bond in susceptible beta-lactam antibiotics, thus conferring resistance to penicillins and cephalosporins. TEM-3 and TEM-4 are capable of hydrolyzing cefotaxime and ceftazidime. TEM-5 is capable of hydrolyzing ceftazidime. TEM-6 is capable of hydrolyzing ceftazidime and aztreonam. TEM-8/CAZ-2, TEM-16/CAZ-7 and TEM-24/CAZ-6 are markedly active against ceftazidime. IRT-4 shows resistance to beta-lactamase inhibitors.
+== 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/er/1erq_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=1erq ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Transition state analogue boronic acid inhibitors mimicking the structures and interactions of good penicillin substrates for the TEM-1 beta-lactamase of Escherchia coli were designed using graphic analyses based on the enzyme's 1.7 A crystallographic structure. The synthesis of two of these transition state analogues, (1R)-1-phenylacetamido-2-(3-carboxyphenyl)ethylboronic acid (1) and (1R)-1-acetamido-2-(3-carboxy-2-hydroxyphenyl)ethylboronic acid (2), is reported. Kinetic measurements show that, as designed, compounds 1 and 2 are highly effective deacylation transition state analogue inhibitors of TEM-1 beta-lactamase, with inhibition constants of 5.9 and 13 nM, respectively. These values identify them as among the most potent competitive inhibitors yet reported for a beta-lactamase. The best inhibitor of the current series was (1R)-1-phenylacetamido-2-(3-carboxyphenyl)ethylboronic acid (1, K(I) = 5.9 nM), which resembles most closely the best known substrate of TEM-1, benzylpenicillin (penicillin G). The high-resolution crystallographic structures of these two inhibitors covalently bound to TEM-1 are also described. In addition to verifying the design features, these two structures show interesting and unanticipated changes in the active site area, including strong hydrogen bond formation, water displacement, and rearrangement of side chains. The structures provide new insights into the further design of this potent class of beta-lactamase inhibitors.
-===X-RAY CRYSTAL STRUCTURE OF TEM-1 BETA LACTAMASE IN COMPLEX WITH A DESIGNED BORONIC ACID INHIBITOR (1R)-1-ACETAMIDO-2-(3-CARBOXY-2-HYDROXYPHENYL)ETHYL BORONIC ACID===
+Structure-based design guides the improved efficacy of deacylation transition state analogue inhibitors of TEM-1 beta-Lactamase(,).,Ness S, Martin R, Kindler AM, Paetzel M, Gold M, Jensen SE, Jones JB, Strynadka NC Biochemistry. 2000 May 9;39(18):5312-21. PMID:10820001<ref>PMID:10820001</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1erq" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_10820001}}, adds the Publication Abstract to the page
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 10820001 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_10820001}}
+__TOC__
+</StructureSection>
-==About this Structure==
-ERQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ERQ OCA].
-==Reference==
-Structure-based design guides the improved efficacy of deacylation transition state analogue inhibitors of TEM-1 beta-Lactamase(,)., Ness S, Martin R, Kindler AM, Paetzel M, Gold M, Jensen SE, Jones JB, Strynadka NC, Biochemistry. 2000 May 9;39(18):5312-21. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10820001 10820001]
-[[Category: Beta-lactamase]]
 [[Category: Escherichia coli]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Gold, M.]]
+[[Category: Gold M]]
-[[Category: Jones, J B.]]
+[[Category: Jones JB]]
-[[Category: Kindler, A M.]]
+[[Category: Kindler AM]]
-[[Category: Martin, R.]]
+[[Category: Martin R]]
-[[Category: Ness, S.]]
+[[Category: Ness S]]
-[[Category: Paetzel, M.]]
+[[Category: Paetzel M]]
-[[Category: Strynadka, N C.J.]]
+[[Category: Strynadka NCJ]]
-[[Category: Beta-lactamase]]
-[[Category: Boronate inhibitor]]
-[[Category: Structure-based design]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul  1 01:46:19 2008''