2fu9: Difference between revisions

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[[Image:2fu9.jpg|left|200px]]


{{Structure
==Zinc-beta-lactamase L1 from stenotrophomonas maltophilia (mp2 inhibitor complex)==
|PDB= 2fu9 |SIZE=350|CAPTION= <scene name='initialview01'>2fu9</scene>, resolution 1.80&Aring;
<StructureSection load='2fu9' size='340' side='right'caption='[[2fu9]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MP2:N-[(BENZYLOXY)CARBONYL]-L-CYSTEINYLGLYCINE'>MP2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
<table><tr><td colspan='2'>[[2fu9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Stenotrophomonas_maltophilia Stenotrophomonas maltophilia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FU9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FU9 FirstGlance]. <br>
|ACTIVITY= <span class='plainlinks'>[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] </span>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
|GENE= L1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=40324 Stenotrophomonas maltophilia])
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MP2:N-[(BENZYLOXY)CARBONYL]-L-CYSTEINYLGLYCINE'>MP2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2fu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fu9 OCA], [https://pdbe.org/2fu9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fu9 RCSB], [https://www.ebi.ac.uk/pdbsum/2fu9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fu9 ProSAT]</span></td></tr>
|RELATEDENTRY=[[2fm6|2FM6]], [[2fu6|2FU6]], [[2fu7|2FU7]], [[2fu8|2FU8]]
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fu9 OCA], [http://www.ebi.ac.uk/pdbsum/2fu9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fu9 RCSB]</span>
== Function ==
}}
[https://www.uniprot.org/uniprot/BLA1_STEMA BLA1_STEMA] Has a high activity against imipenem.
== 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/fu/2fu9_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=2fu9 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
One mechanism by which bacteria can escape the action of beta-lactam antibiotics is the production of metallo-beta-lactamases. Inhibition of these enzymes should restore the action of these widely used antibiotics. The tetrameric enzyme L1 from Stenotrophomonas maltophilia was used as a model system to determine a series of high-resolution crystal structures of apo, mono and bi-metal substituted proteins as well as protein-inhibitor complexes. Unexpectedly, although the apo structure revealed only few significant structural differences from the holo structure, some inhibitors were shown to induce amino acid side-chain rotations in the tightly packed active site. Moreover, one inhibitor employs a new binding mode in order to interact with the di-zinc center. This structural information could prove essential in the process of elucidation of the mode of interaction between a putative lead compound and metallo-beta-lactamases, one of the main steps in structure-based drug design.


'''Zinc-beta-lactamase L1 from stenotrophomonas maltophilia (mp2 inhibitor complex)'''
Structural insights into the design of inhibitors for the L1 metallo-beta-lactamase from Stenotrophomonas maltophilia.,Nauton L, Kahn R, Garau G, Hernandez JF, Dideberg O J Mol Biol. 2008 Jan 4;375(1):257-69. Epub 2007 Oct 22. PMID:17999929<ref>PMID:17999929</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2fu9" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
The 3-D structure of Bacillus cereus (569/H/9) beta-lactamase (EC 3.5.2.6), which catalyses the hydrolysis of nearly all beta-lactams, has been solved at 2.5 A resolution by the multiple isomorphous replacement method, with density modification and phase combination, from crystals of the native protein and of a specially designed mutant (T97C). The current model includes 212 of the 227 amino acid residues, the zinc ion and 10 water molecules. The protein is folded into a beta beta sandwich with helices on each external face. To our knowledge, this fold has never been observed. An approximate internal molecular symmetry is found, with a 2-fold axis passing roughly through the zinc ion and suggesting a possible gene duplication. The active site is located at one edge of the beta beta sandwich and near the N-terminal end of a helix. The zinc ion is coordinated by three histidine residues (86, 88 and 149) and a water molecule. A sequence comparison of the relevant metallo-beta-lactamases, based on this protein structure, highlights a few well-conserved amino acid residues. The structure shows that most of these residues are in the active site. Among these, aspartic acid 90 and histidine 210 participate in a proposed catalytic mechanism for beta-lactam hydrolysis.
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
 
== References ==
==About this Structure==
<references/>
2FU9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Stenotrophomonas_maltophilia Stenotrophomonas maltophilia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FU9 OCA].
__TOC__
 
</StructureSection>
==Reference==
[[Category: Large Structures]]
The 3-D structure of a zinc metallo-beta-lactamase from Bacillus cereus reveals a new type of protein fold., Carfi A, Pares S, Duee E, Galleni M, Duez C, Frere JM, Dideberg O, EMBO J. 1995 Oct 16;14(20):4914-21. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/7588620 7588620]
[[Category: Beta-lactamase]]
[[Category: Single protein]]
[[Category: Stenotrophomonas maltophilia]]
[[Category: Stenotrophomonas maltophilia]]
[[Category: Dideberg, O.]]
[[Category: Dideberg O]]
[[Category: Garau, G.]]
[[Category: Garau G]]
[[Category: Kahn, R.]]
[[Category: Kahn R]]
[[Category: Nauton, L.]]
[[Category: Nauton L]]
[[Category: beta]]
[[Category: hydrolase]]
[[Category: inhibitor]]
[[Category: lactamase]]
[[Category: metallo]]
[[Category: zn]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:07:50 2008''

Latest revision as of 11:00, 30 October 2024

Zinc-beta-lactamase L1 from stenotrophomonas maltophilia (mp2 inhibitor complex)Zinc-beta-lactamase L1 from stenotrophomonas maltophilia (mp2 inhibitor complex)

Structural highlights

2fu9 is a 2 chain structure with sequence from Stenotrophomonas maltophilia. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.8Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BLA1_STEMA Has a high activity against imipenem.

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

One mechanism by which bacteria can escape the action of beta-lactam antibiotics is the production of metallo-beta-lactamases. Inhibition of these enzymes should restore the action of these widely used antibiotics. The tetrameric enzyme L1 from Stenotrophomonas maltophilia was used as a model system to determine a series of high-resolution crystal structures of apo, mono and bi-metal substituted proteins as well as protein-inhibitor complexes. Unexpectedly, although the apo structure revealed only few significant structural differences from the holo structure, some inhibitors were shown to induce amino acid side-chain rotations in the tightly packed active site. Moreover, one inhibitor employs a new binding mode in order to interact with the di-zinc center. This structural information could prove essential in the process of elucidation of the mode of interaction between a putative lead compound and metallo-beta-lactamases, one of the main steps in structure-based drug design.

Structural insights into the design of inhibitors for the L1 metallo-beta-lactamase from Stenotrophomonas maltophilia.,Nauton L, Kahn R, Garau G, Hernandez JF, Dideberg O J Mol Biol. 2008 Jan 4;375(1):257-69. Epub 2007 Oct 22. PMID:17999929[1]

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

See Also

References

  1. ↑ Nauton L, Kahn R, Garau G, Hernandez JF, Dideberg O. Structural insights into the design of inhibitors for the L1 metallo-beta-lactamase from Stenotrophomonas maltophilia. J Mol Biol. 2008 Jan 4;375(1):257-69. Epub 2007 Oct 22. PMID:17999929 doi:10.1016/j.jmb.2007.10.036

2fu9, resolution 1.80Å

Drag the structure with the mouse to rotate

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