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== | ==Crystal structure of PBP1a from drug-resistant strain 5204 from Streptococcus pneumoniae== | ||
<StructureSection load='2v2f' size='340' side='right'caption='[[2v2f]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2v2f]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V2F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V2F 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]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BA:BARIUM+ION'>BA</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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=2v2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v2f OCA], [https://pdbe.org/2v2f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v2f RCSB], [https://www.ebi.ac.uk/pdbsum/2v2f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v2f ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9RET4_STREE Q9RET4_STREE] | |||
== 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/v2/2v2f_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2v2f ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The development of high level beta-lactam resistance in the pneumococcus requires the expression of an altered form of PBP1a, in addition to modified forms of PBP2b and PBP2x, which are necessary for the appearance of low levels of resistance. Here, we present the crystal structure of a soluble form of PBP1a from the highly resistant Streptococcus pneumoniae strain 5204 (minimal inhibitory concentration of cefotaxime is 12 mg.liter(-1)). Mutations T371A, which is adjacent to the catalytic nucleophile Ser(370), and TSQF(574-577)NTGY, which lie in a loop bordering the active site cleft, were investigated by site-directed mutagenesis. The consequences of these substitutions on reaction kinetics with beta-lactams were probed in vitro, and their effect on resistance was measured in vivo. The results are interpreted in the framework of the crystal structure, which displays a narrower, discontinuous active site cavity, compared with that of PBP1a from the beta-lactam susceptible strain R6, as well as a reorientation of the catalytic Ser(370). | The development of high level beta-lactam resistance in the pneumococcus requires the expression of an altered form of PBP1a, in addition to modified forms of PBP2b and PBP2x, which are necessary for the appearance of low levels of resistance. Here, we present the crystal structure of a soluble form of PBP1a from the highly resistant Streptococcus pneumoniae strain 5204 (minimal inhibitory concentration of cefotaxime is 12 mg.liter(-1)). Mutations T371A, which is adjacent to the catalytic nucleophile Ser(370), and TSQF(574-577)NTGY, which lie in a loop bordering the active site cleft, were investigated by site-directed mutagenesis. The consequences of these substitutions on reaction kinetics with beta-lactams were probed in vitro, and their effect on resistance was measured in vivo. The results are interpreted in the framework of the crystal structure, which displays a narrower, discontinuous active site cavity, compared with that of PBP1a from the beta-lactam susceptible strain R6, as well as a reorientation of the catalytic Ser(370). | ||
Common Alterations in PBP1a from Resistant Streptococcus pneumoniae Decrease Its Reactivity toward {beta}-Lactams: STRUCTURAL INSIGHTS.,Job V, Carapito R, Vernet T, Dessen A, Zapun A J Biol Chem. 2008 Feb 22;283(8):4886-4894. Epub 2007 Nov 30. PMID:18055459<ref>PMID:18055459</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[ | <div class="pdbe-citations 2v2f" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
==See Also== | |||
*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Streptococcus pneumoniae]] | [[Category: Streptococcus pneumoniae]] | ||
[[Category: Carapito | [[Category: Carapito R]] | ||
[[Category: Dessen | [[Category: Dessen A]] | ||
[[Category: Dideberg | [[Category: Dideberg O]] | ||
[[Category: Job | [[Category: Job V]] | ||
[[Category: Vernet | [[Category: Vernet T]] | ||
[[Category: Zapun | [[Category: Zapun A]] | ||
Latest revision as of 18:02, 13 December 2023
Crystal structure of PBP1a from drug-resistant strain 5204 from Streptococcus pneumoniaeCrystal structure of PBP1a from drug-resistant strain 5204 from Streptococcus pneumoniae
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe development of high level beta-lactam resistance in the pneumococcus requires the expression of an altered form of PBP1a, in addition to modified forms of PBP2b and PBP2x, which are necessary for the appearance of low levels of resistance. Here, we present the crystal structure of a soluble form of PBP1a from the highly resistant Streptococcus pneumoniae strain 5204 (minimal inhibitory concentration of cefotaxime is 12 mg.liter(-1)). Mutations T371A, which is adjacent to the catalytic nucleophile Ser(370), and TSQF(574-577)NTGY, which lie in a loop bordering the active site cleft, were investigated by site-directed mutagenesis. The consequences of these substitutions on reaction kinetics with beta-lactams were probed in vitro, and their effect on resistance was measured in vivo. The results are interpreted in the framework of the crystal structure, which displays a narrower, discontinuous active site cavity, compared with that of PBP1a from the beta-lactam susceptible strain R6, as well as a reorientation of the catalytic Ser(370). Common Alterations in PBP1a from Resistant Streptococcus pneumoniae Decrease Its Reactivity toward {beta}-Lactams: STRUCTURAL INSIGHTS.,Job V, Carapito R, Vernet T, Dessen A, Zapun A J Biol Chem. 2008 Feb 22;283(8):4886-4894. Epub 2007 Nov 30. PMID:18055459[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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