3d4f: Difference between revisions

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<StructureSection load='3d4f' size='340' side='right'caption='[[3d4f]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
<StructureSection load='3d4f' size='340' side='right'caption='[[3d4f]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3d4f]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D4F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D4F FirstGlance]. <br>
<table><tr><td colspan='2'>[[3d4f]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D4F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D4F FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LN1:(3R)-4-{[(3,4-DIHYDROXYPHENYL)ACETYL]OXY}-N-(2-FORMYLINDOLIZIN-3-YL)-3-SULFINO-D-VALINE'>LN1</scene>, <scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1shv|1shv]], [[1ga0|1ga0]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LN1:(3R)-4-{[(3,4-DIHYDROXYPHENYL)ACETYL]OXY}-N-(2-FORMYLINDOLIZIN-3-YL)-3-SULFINO-D-VALINE'>LN1</scene>, <scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla, shv1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 "Bacillus pneumoniae" (Schroeter 1886) Flugge 1886])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></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=3d4f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d4f OCA], [https://pdbe.org/3d4f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d4f RCSB], [https://www.ebi.ac.uk/pdbsum/3d4f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d4f ProSAT]</span></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=3d4f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d4f OCA], [https://pdbe.org/3d4f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d4f RCSB], [https://www.ebi.ac.uk/pdbsum/3d4f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d4f ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BLA1_KLEPN BLA1_KLEPN]
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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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=3d4f ConSurf].
</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=3d4f ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In an effort to devise strategies for overcoming bacterial beta-lactamases, we studied LN-1-255, a 6-alkylidene-2'-substituted penicillin sulfone inhibitor. By possessing a catecholic functionality that resembles a natural bacterial siderophore, LN-1-255 is unique among beta-lactamase inhibitors. LN-1-255 combined with piperacillin was more potent against Escherichia coli DH10B strains bearing bla(SHV) extended-spectrum and inhibitor-resistant beta-lactamases than an equivalent amount of tazobactam and piperacillin. In addition, LN-1-255 significantly enhanced the activity of ceftazidime and cefpirome against extended-spectrum cephalosporin and Sme-1 containing carbapenem-resistant clinical strains. LN-1-255 inhibited SHV-1 and SHV-2 beta-lactamases with nm affinity (K(I) = 110 +/- 10 and 100 +/- 10 nm, respectively). When LN-1-255 inactivated SHV beta-lactamases, a single intermediate was detected by mass spectrometry. The crystal structure of LN-1-255 in complex with SHV-1 was determined at 1.55A resolution. Interestingly, this novel inhibitor forms a bicyclic aromatic intermediate with its carbonyl oxygen pointing out of the oxyanion hole and forming hydrogen bonds with Lys-234 and Ser-130 in the active site. Electron density for the "tail" of LN-1-255 is less ordered and modeled in two conformations. Both conformations have the LN-1-255 carboxyl group interacting with Arg-244, yet the remaining tails of the two conformations diverge. The observed presence of the bicyclic aromatic intermediate with its carbonyl oxygen positioned outside of the oxyanion hole provides a rationale for the stability of this inhibitory intermediate. The 2'-substituted penicillin sulfone, LN-1-255, is proving to be an important lead compound for novel beta-lactamase inhibitor design.
Strategic design of an effective beta-lactamase inhibitor: LN-1-255, a 6-alkylidene-2'-substituted penicillin sulfone.,Pattanaik P, Bethel CR, Hujer AM, Hujer KM, Distler AM, Taracila M, Anderson VE, Fritsche TR, Jones RN, Pagadala SR, van den Akker F, Buynak JD, Bonomo RA J Biol Chem. 2009 Jan 9;284(2):945-53. Epub 2008 Oct 27. PMID:18955486<ref>PMID:18955486</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3d4f" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Beta-lactamase]]
[[Category: Klebsiella pneumoniae]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Akker, F van den]]
[[Category: Bethel CR]]
[[Category: Bethel, C R]]
[[Category: Bonomo RA]]
[[Category: Bonomo, R A]]
[[Category: Buynak JD]]
[[Category: Buynak, J D]]
[[Category: Hujer AM]]
[[Category: Hujer, A M]]
[[Category: Pattanaik P]]
[[Category: Pattanaik, P]]
[[Category: Van den Akker F]]
[[Category: Antibiotic resistance]]
[[Category: Beta-lactamase inhibitor]]
[[Category: Drug design]]
[[Category: Hydrolase]]
[[Category: Plasmid]]
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