1g6a: Difference between revisions

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1g6a.gif|left|200px]]<br /><applet load="1g6a" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1g6a, resolution 1.75&Aring;" />
-'''PSE-4 CARBENICILLINASE, R234K MUTANT'''<br />
-==Overview==
+==PSE-4 CARBENICILLINASE, R234K MUTANT==
-PSE-4 is a class A beta-lactamase produced by strains of Pseudomonas, aeruginosa and is highly active for the penicillin derivative, carbenicillin. The crystal structure of the wild-type PSE-4, carbenicillinase has been determined to 1.95 A resolution by molecular, replacement and represents the first structure of a carbenicillinase, published to date. A superposition of the PSE-4 structure with that of, TEM-1 shows a rms deviation of 1.3 A for 263 Calpha atoms. Most, carbenicillinases are unique among class A beta-lactamases in that residue, 234 is an arginine (ABL standard numbering scheme), while in all other, class A enzymes this residue is a lysine. Kinetic characterization of a, R234K PSE-4 mutant reveals a 50-fold reduction in k(cat)/K(m) and confirms, the importance of Arg 234 for carbenicillinase activity. A comparison of, the structure of the R234K mutant refined to 1.75 A resolution with the, wild-type structure shows that Arg 234 stabilizes an alternate, conformation of the Ser 130 side chain, not seen in other class A, beta-lactamase structures. Our molecular modeling studies suggest that the, position of a bound carbenicillin would be shifted relative to that of a, bound benzylpenicillin in order to avoid a steric clash between the, carbenicillin alpha-carboxylate group and the conserved side chain of Asn, 170. The alternate conformation of the catalytic Ser 130 in wild-type, PSE-4 may be involved in accommodating this shift in the bound substrate, position.
+<StructureSection load='1g6a' size='340' side='right'caption='[[1g6a]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1g6a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G6A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1G6A 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]] 1.75&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1g6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g6a OCA], [https://pdbe.org/1g6a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1g6a RCSB], [https://www.ebi.ac.uk/pdbsum/1g6a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1g6a ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/BLP4_PSEAI BLP4_PSEAI] Hydrolyzes both carbenicillin and oxacillin.
+== 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/g6/1g6a_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=1g6a ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+PSE-4 is a class A beta-lactamase produced by strains of Pseudomonas aeruginosa and is highly active for the penicillin derivative carbenicillin. The crystal structure of the wild-type PSE-4 carbenicillinase has been determined to 1.95 A resolution by molecular replacement and represents the first structure of a carbenicillinase published to date. A superposition of the PSE-4 structure with that of TEM-1 shows a rms deviation of 1.3 A for 263 Calpha atoms. Most carbenicillinases are unique among class A beta-lactamases in that residue 234 is an arginine (ABL standard numbering scheme), while in all other class A enzymes this residue is a lysine. Kinetic characterization of a R234K PSE-4 mutant reveals a 50-fold reduction in k(cat)/K(m) and confirms the importance of Arg 234 for carbenicillinase activity. A comparison of the structure of the R234K mutant refined to 1.75 A resolution with the wild-type structure shows that Arg 234 stabilizes an alternate conformation of the Ser 130 side chain, not seen in other class A beta-lactamase structures. Our molecular modeling studies suggest that the position of a bound carbenicillin would be shifted relative to that of a bound benzylpenicillin in order to avoid a steric clash between the carbenicillin alpha-carboxylate group and the conserved side chain of Asn 170. The alternate conformation of the catalytic Ser 130 in wild-type PSE-4 may be involved in accommodating this shift in the bound substrate position.
-==About this Structure==
+Insights into the molecular basis for the carbenicillinase activity of PSE-4 beta-lactamase from crystallographic and kinetic studies.,Lim D, Sanschagrin F, Passmore L, De Castro L, Levesque RC, Strynadka NC Biochemistry. 2001 Jan 16;40(2):395-402. PMID:11148033<ref>PMID:11148033</ref>
-G6A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1G6A OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Insights into the molecular basis for the carbenicillinase activity of PSE-4 beta-lactamase from crystallographic and kinetic studies., Lim D, Sanschagrin F, Passmore L, De Castro L, Levesque RC, Strynadka NC, Biochemistry. 2001 Jan 16;40(2):395-402. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11148033 11148033]
+</div>
-[[Category: Beta-lactamase]]
+<div class="pdbe-citations 1g6a" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Pseudomonas aeruginosa]]
-[[Category: Single protein]]
+[[Category: De Castro L]]
-[[Category: Castro, L.De.]]
+[[Category: Levesque RC]]
-[[Category: Levesque, R.C.]]
+[[Category: Lim D]]
-[[Category: Lim, D.]]
+[[Category: Passmore L]]
-[[Category: Passmore, L.]]
+[[Category: Sanschagrin F]]
-[[Category: Sanschagrin, F.]]
+[[Category: Strynadka NCJ]]
-[[Category: Strynadka, N.C.J.]]
-[[Category: SO4]]
-[[Category: carbenicillinase]]
-[[Category: class a beta-lactamase]]
-[[Category: r234k mutant]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 15:45:00 2007''