View source for 3d41


==Crystal structure of fosfomycin resistance kinase FomA from Streptomyces wedmorensis complexed with MgAMPPNP and fosfomycin==
<StructureSection load='3d41' size='340' side='right'caption='[[3d41]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3d41]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_wedmorensis Streptomyces wedmorensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D41 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D41 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=FCN:FOSFOMYCIN'>FCN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=3d41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d41 OCA], [https://pdbe.org/3d41 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d41 RCSB], [https://www.ebi.ac.uk/pdbsum/3d41 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d41 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q56187_STRWE Q56187_STRWE] 
== 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/d4/3d41_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=3d41 ConSurf].
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== Publication Abstract from PubMed ==
The fosfomycin resistance protein FomA inactivates fosfomycin by phosphorylation of the phosphonate group of the antibiotic in the presence of ATP and Mg(II). We report the crystal structure of FomA from the fosfomycin biosynthetic gene cluster of Streptomyces wedmorensis in complex with diphosphate and in ternary complex with the nonhydrolyzable ATP analog adenosine 5'-(beta,gamma-imido)-triphosphate (AMPPNP), Mg(II), and fosfomycin, at 1.53 and 2.2 angstroms resolution, respectively. The polypeptide exhibits an open alphabetaalpha sandwich fold characteristic for the amino acid kinase family of enzymes. The diphosphate complex shows significant disorder in loops surrounding the active site. As a result, the nucleotide-binding site is wide open. Binding of the substrates is followed by the partial closure of the active site and ordering of the alpha2-helix. Structural comparison with N-acetyl-L-glutamate kinase shows several similarities in the site of phosphoryl transfer: 1) preservation of architecture of the catalytical amino acids of N-acetyl-L-glutamate kinase (Lys9, Lys216, and Asp150 in FomA); 2) good superposition of the phosphate acceptor groups of the substrates, and 3) good superposition of the diphosphate molecule with the beta- and gamma-phosphates of AMPPNP, suggesting that the reaction could proceed by an associative in-line mechanism. However, differences in conformations of the triphosphate moiety of AMPPNP molecules, the long distance (5.1 angstroms) between the phosphate acceptor and donor groups in FomA, and involvement of Lys18 instead of Lys9 in binding with the gamma-phosphate may indicate a different reaction mechanism. The present work identifies the active site residues of FomA responsible for substrate binding and specificity and proposes their roles in catalysis.

Crystal structure of fosfomycin resistance kinase FomA from Streptomyces wedmorensis.,Pakhomova S, Bartlett SG, Augustus A, Kuzuyama T, Newcomer ME J Biol Chem. 2008 Oct 17;283(42):28518-26. Epub 2008 Aug 12. PMID:18701452<ref>PMID:18701452</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3d41" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces wedmorensis]]
[[Category: Augustus A]]
[[Category: Bartlett SG]]
[[Category: Kuzuyama T]]
[[Category: Newcomer ME]]
[[Category: Pakhomova S]]