View source for 1mpl


==CRYSTAL STRUCTURE OF PHOSPHONATE-INHIBITED D-ALA-D-ALA PEPTIDASE REVEALS AN ANALOG OF A TETRAHEDRAL TRANSITION STATE==
<StructureSection load='1mpl' size='340' side='right'caption='[[1mpl]], [[Resolution|resolution]] 1.12&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1mpl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp._R61 Streptomyces sp. R61]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MPL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MPL 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]] 1.12&#8491;</td></tr>
<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=RE1:GLYCYL-L-A-AMINOPIMELYL-E-(D-2-AMINOETHYL)PHOSPHONATE'>RE1</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=1mpl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mpl OCA], [https://pdbe.org/1mpl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mpl RCSB], [https://www.ebi.ac.uk/pdbsum/1mpl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mpl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DAC_STRSR DAC_STRSR] Catalyzes distinct carboxypeptidation and transpeptidation reactions during the last stages of wall peptidoglycan synthesis. Mistaking a beta-lactam antibiotic molecule for a normal substrate (i.e. a D-alanyl-D-alanine-terminated peptide), it becomes immobilized in the form of a long-lived, serine-ester-linked acyl enzyme and thus behave as penicillin-binding protein (PBP).
== 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/mp/1mpl_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=1mpl ConSurf].
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== Publication Abstract from PubMed ==
D-Alanyl-D-alanine carboxypeptidase/transpeptidases (DD-peptidases) are beta-lactam-sensitive enzymes that are responsible for the final peptidoglycan cross-linking step in bacterial cell wall biosynthesis. A highly specific tripeptide phosphonate inhibitor was designed with a side chain corresponding to a portion of the Streptomyces R61 peptidoglycan. This compound was found to be a slow, irreversible inactivator of the DD-peptidase. Molecular modeling suggested that although a pentacoordinated intermediate of the phosphonylation reaction would not interact strongly with the enzyme, a tetracoordinated phosphonyl enzyme might be analogous to a transition state in the reaction with peptide substrates. To investigate this possibility, the crystal structure of the phosphonyl enzyme was determined. The 1.1 A resolution structure shows that the inhibitor has phosphonylated the catalytic serine (Ser62). One of the phosphonyl oxygens is noncovalently bound in the oxyanion hole, while the other is solvated by two water molecules. The conserved hydroxyl group of Tyr159 forms a strong hydrogen bond with the latter oxygen atom (2.77 A). This arrangement is interpreted as being analogous to the transition state for the formation of the tetrahedral intermediate in the deacylation step of the carboxypeptidase reaction. The proximity of Tyr159 to the solvated phosphonyl oxygen suggests that the tyrosine anion acts as a general base for deacylation. This transition state analogue structure is compared to the structures of noncovalent DD-peptidase reaction intermediates and phosphonylated beta-lactamases. These comparisons show that specific substrate binding to the peptidase induces a conformational change in the active site that places Ser62 in an optimal position for catalysis. This activated conformation relaxes as the reaction proceeds.

The crystal structure of phosphonate-inhibited D-Ala-D-Ala peptidase reveals an analogue of a tetrahedral transition state.,Silvaggi NR, Anderson JW, Brinsmade SR, Pratt RF, Kelly JA Biochemistry. 2003 Feb 11;42(5):1199-208. PMID:12564922<ref>PMID:12564922</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 1mpl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces sp. R61]]
[[Category: Anderson JW]]
[[Category: Brinsmade SR]]
[[Category: Kelly JA]]
[[Category: Pratt RF]]
[[Category: Silvaggi NR]]