2xdm

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of a complex between Actinomadura R39 DD peptidase and a peptidoglycan mimetic boronate inhibitor

Structural highlights

2xdm is a 4 chain structure with sequence from Actinomadura sp. R39. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DAC_ACTSP Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors.

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 Actinomadura R39 dd-peptidase is a bacterial low molecular weight class C penicillin-binding protein. It has previously been shown to catalyze hydrolysis and aminolysis of small d-alanyl-d-alanine terminating peptides, especially those with a side chain that mimics the amino terminus of the stem peptide precursor to the bacterial cell wall. This paper describes the synthesis of (d-alpha-aminopimelylamino)-d-1-ethylboronic acid, designed to be a peptidoglycan-mimetic transition state analogue inhibitor of the R39 dd-peptidase. The boronate was found to be a potent inhibitor of the peptidase with a K(i) value of 32 +/- 6 nM. Since it binds some 30 times more strongly than the analogous peptide substrate, the boronate may well be a transition state analogue. A crystal structure of the inhibitory complex shows the boronate covalently bound to the nucleophilic active site Ser 49. The aminopimelyl side chain is bound into the site previously identified as specific for this moiety. One boronate oxygen is held in the oxyanion hole; the other, occupying the leaving group site of acylation or the nucleophile site of deacylation, appears to be hydrogen-bonded to the hydroxyl group of Ser 298. The Ser 49 oxygen appears to be hydrogen bonded to Lys 52. If it is assumed that this structure does resemble a high-energy tetrahedral intermediate in catalysis, it seems likely that Ser 298 participates as part of a proton transfer chain initiated by Lys 52 or Lys 410 as the primary proton donor/acceptor. The structure, therefore, supports a particular class of mechanism that employs this proton transfer device.

Crystal Structure of a Complex between the Actinomadura R39 dd-Peptidase and a Peptidoglycan-mimetic Boronate Inhibitor: Interpretation of a Transition State Analogue in Terms of Catalytic Mechanism.,Dzhekieva L, Rocaboy M, Kerff F, Charlier P, Sauvage E, Pratt RF Biochemistry. 2010 Jul 7. PMID:20608745^[1]

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

References

↑ Dzhekieva L, Rocaboy M, Kerff F, Charlier P, Sauvage E, Pratt RF. Crystal Structure of a Complex between the Actinomadura R39 dd-Peptidase and a Peptidoglycan-mimetic Boronate Inhibitor: Interpretation of a Transition State Analogue in Terms of Catalytic Mechanism. Biochemistry. 2010 Jul 7. PMID:20608745 doi:10.1021/bi100757c

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2xdm"

@@ Line 1: / Line 1: @@
 ==Crystal structure of a complex between Actinomadura R39 DD peptidase and a peptidoglycan mimetic boronate inhibitor==
-<StructureSection load='2xdm' size='340' side='right' caption='[[2xdm]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='2xdm' size='340' side='right'caption='[[2xdm]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2xdm]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Actinomadura Actinomadura]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XDM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XDM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2xdm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Actinomadura_sp._R39 Actinomadura sp. R39]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XDM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XDM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BO8:(D-ALPHA-AMINOPIMELYLAMINO)-D-1-ETHYLBORONIC+ACID'>BO8</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.4&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1w79|1w79]], [[2wke|2wke]], [[2vgj|2vgj]], [[1w8q|1w8q]], [[2wix|2wix]], [[1w8y|1w8y]], [[2vgk|2vgk]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BO8:(D-ALPHA-AMINOPIMELYLAMINO)-D-1-ETHYLBORONIC+ACID'>BO8</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Serine-type_D-Ala-D-Ala_carboxypeptidase Serine-type D-Ala-D-Ala carboxypeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.16.4 3.4.16.4] </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=2xdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xdm OCA], [https://pdbe.org/2xdm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xdm RCSB], [https://www.ebi.ac.uk/pdbsum/2xdm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xdm ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xdm OCA], [http://pdbe.org/2xdm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xdm RCSB], [http://www.ebi.ac.uk/pdbsum/2xdm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xdm ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/DAC_ACTSP DAC_ACTSP]] Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors.
+[https://www.uniprot.org/uniprot/DAC_ACTSP DAC_ACTSP] Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 16: / Line 15: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xd/2xdm_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 32: / Line 31: @@
 ==See Also==
-*[[Carboxypeptidase|Carboxypeptidase]]
+*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
+*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Actinomadura]]
+[[Category: Actinomadura sp. R39]]
-[[Category: Serine-type D-Ala-D-Ala carboxypeptidase]]
+[[Category: Large Structures]]
-[[Category: Charlier, P]]
+[[Category: Charlier P]]
-[[Category: Herman, R]]
+[[Category: Herman R]]
-[[Category: Kerff, F]]
+[[Category: Kerff F]]
-[[Category: Rocaboy, M]]
+[[Category: Rocaboy M]]
-[[Category: Sauvage, E]]
+[[Category: Sauvage E]]
-[[Category: Boronic acid]]
-[[Category: Hydrolase]]
-[[Category: Hydrolase-inhibitor complex]]
-[[Category: Peptidoglycan]]

2xdm

From Proteopedia

Current revision

Crystal structure of a complex between Actinomadura R39 DD peptidase and a peptidoglycan mimetic boronate inhibitor

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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