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[[Image:1xx2.png|left|200px]]


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==Refinement of P99 beta-lactamase from Enterobacter cloacae==
The line below this paragraph, containing "STRUCTURE_1xx2", creates the "Structure Box" on the page.
<StructureSection load='1xx2' size='340' side='right'caption='[[1xx2]], [[Resolution|resolution]] 1.88&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'>[[1xx2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterobacter_cloacae Enterobacter cloacae]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2blt 2blt]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XX2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XX2 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]] 1.88&#8491;</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=1xx2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xx2 OCA], [https://pdbe.org/1xx2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xx2 RCSB], [https://www.ebi.ac.uk/pdbsum/1xx2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xx2 ProSAT]</span></td></tr>
{{STRUCTURE_1xx2|  PDB=1xx2  |  SCENE=  }}
</table>
== Function ==
[https://www.uniprot.org/uniprot/AMPC_ENTCL AMPC_ENTCL] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
== 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/xx/1xx2_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=1xx2 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The crystal structure of a complex formed on reaction of the Enterobacter cloacae P99 cephalosporinase (beta-lactamase) with a phosphonate monoester inhibitor, m-carboxyphenyl [[N-[(p-iodophenyl)acetyl]amino]methyl]phosphonate, has been obtained at 2.3-A resolution. The structure shows that the inhibitor has phosphonylated the active site serine (Ser64) with loss of the m-carboxyphenol leaving group. The inhibitor is positioned in the active site in a way that can be interpreted in terms of a transition-state analog. The arylacetamido side chain is placed as anticipated from analogous beta-lactamoyl complexes of penicillin-recognizing enzymes, with the amino group hydrogen-bonded to the backbone carbonyl of Ser318 (of the B3 beta-strand) and to the amides of Gln120 and Asn152. There is support in the asymmetry of the hydrogen bonding of this side chain to the protein and in the 2-fold disorder of the benzyl group for the considerable breadth in substrate specificity exhibited by class C beta-lactamases. One phosphonyl oxygen atom is in the oxyanion hole, hydrogen-bonded to main-chain NH groups of Ser318 and Ser64, while the other oxygen is solvated, not within hydrogen-bonding distance of any amino acid side chain. The closest active site functional group to the solvated oxygen atom is the Tyr150 hydroxyl group (3.4A); Lys67 and Lys315 are quite distant (4.3 and 5.7 A, respectively). Rather, Tyr150 and Lys67 are more closely associated with Ser64O gamma (2.9 and 3.3 A). This arrangement is interpreted in terms of the transition state for breakdown of the tetrahedral intermediate in the deacylation step of catalysis, where the Tyr150 phenol seems the most likely general acid. Thus, Tyr150, as the phenoxide anion, would be the general base catalyst in acylation, as proposed by Oefner et al. [Nature (1990) 343, 284-288]. The structure is compared with that of a similar phosphonate derivative of a class A beta-lactamase [Chen et al. (1993) J. Mol. Biol. 234, 165-178], and mechanistic comparisons are made. The sensitivity of serine beta-lactamases, as opposed to serine proteinases, toward inhibition by phosphonate monoanions is supported by electrostatic calculations showing a net positive potential only in the catalytic sites of the beta-lactamases.


===Refinement of P99 beta-lactamase from Enterobacter cloacae===
Crystallographic structure of a phosphonate derivative of the Enterobacter cloacae P99 cephalosporinase: mechanistic interpretation of a beta-lactamase transition-state analog.,Lobkovsky E, Billings EM, Moews PC, Rahil J, Pratt RF, Knox JR Biochemistry. 1994 Jun 7;33(22):6762-72. PMID:8204611<ref>PMID:8204611</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1xx2" style="background-color:#fffaf0;"></div>


==About this Structure==
==See Also==
1XX2 is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Enterobacter_cloacae Enterobacter cloacae]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2blt 2blt]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XX2 OCA].
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
[[Category: Beta-lactamase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Enterobacter cloacae]]
[[Category: Enterobacter cloacae]]
[[Category: Knox, J R.]]
[[Category: Large Structures]]
[[Category: Sun, T.]]
[[Category: Knox JR]]
[[Category: Ampc]]
[[Category: Sun T]]
[[Category: Antibiotic resistance]]
[[Category: Cephalosporinase]]
[[Category: Class c beta-lactamase]]
[[Category: Enterobacter cloacae]]
[[Category: Penicillinase]]
[[Category: Serine hydrolase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 01:25:26 2009''

Latest revision as of 09:50, 23 August 2023

Refinement of P99 beta-lactamase from Enterobacter cloacaeRefinement of P99 beta-lactamase from Enterobacter cloacae

Structural highlights

1xx2 is a 2 chain structure with sequence from Enterobacter cloacae. This structure supersedes the now removed PDB entry 2blt. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.88Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AMPC_ENTCL This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The crystal structure of a complex formed on reaction of the Enterobacter cloacae P99 cephalosporinase (beta-lactamase) with a phosphonate monoester inhibitor, m-carboxyphenyl [[N-[(p-iodophenyl)acetyl]amino]methyl]phosphonate, has been obtained at 2.3-A resolution. The structure shows that the inhibitor has phosphonylated the active site serine (Ser64) with loss of the m-carboxyphenol leaving group. The inhibitor is positioned in the active site in a way that can be interpreted in terms of a transition-state analog. The arylacetamido side chain is placed as anticipated from analogous beta-lactamoyl complexes of penicillin-recognizing enzymes, with the amino group hydrogen-bonded to the backbone carbonyl of Ser318 (of the B3 beta-strand) and to the amides of Gln120 and Asn152. There is support in the asymmetry of the hydrogen bonding of this side chain to the protein and in the 2-fold disorder of the benzyl group for the considerable breadth in substrate specificity exhibited by class C beta-lactamases. One phosphonyl oxygen atom is in the oxyanion hole, hydrogen-bonded to main-chain NH groups of Ser318 and Ser64, while the other oxygen is solvated, not within hydrogen-bonding distance of any amino acid side chain. The closest active site functional group to the solvated oxygen atom is the Tyr150 hydroxyl group (3.4A); Lys67 and Lys315 are quite distant (4.3 and 5.7 A, respectively). Rather, Tyr150 and Lys67 are more closely associated with Ser64O gamma (2.9 and 3.3 A). This arrangement is interpreted in terms of the transition state for breakdown of the tetrahedral intermediate in the deacylation step of catalysis, where the Tyr150 phenol seems the most likely general acid. Thus, Tyr150, as the phenoxide anion, would be the general base catalyst in acylation, as proposed by Oefner et al. [Nature (1990) 343, 284-288]. The structure is compared with that of a similar phosphonate derivative of a class A beta-lactamase [Chen et al. (1993) J. Mol. Biol. 234, 165-178], and mechanistic comparisons are made. The sensitivity of serine beta-lactamases, as opposed to serine proteinases, toward inhibition by phosphonate monoanions is supported by electrostatic calculations showing a net positive potential only in the catalytic sites of the beta-lactamases.

Crystallographic structure of a phosphonate derivative of the Enterobacter cloacae P99 cephalosporinase: mechanistic interpretation of a beta-lactamase transition-state analog.,Lobkovsky E, Billings EM, Moews PC, Rahil J, Pratt RF, Knox JR Biochemistry. 1994 Jun 7;33(22):6762-72. PMID:8204611[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Lobkovsky E, Billings EM, Moews PC, Rahil J, Pratt RF, Knox JR. Crystallographic structure of a phosphonate derivative of the Enterobacter cloacae P99 cephalosporinase: mechanistic interpretation of a beta-lactamase transition-state analog. Biochemistry. 1994 Jun 7;33(22):6762-72. PMID:8204611

1xx2, resolution 1.88Å

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