View source for 6jtc


==Crystal structure of dipeptidyl peptidase 11 (DPP11) with SH-5 from Porphyromonas gingivalis (Space)==
<StructureSection load='6jtc' size='340' side='right'caption='[[6jtc]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6jtc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Porphyromonas_gingivalis_ATCC_33277 Porphyromonas gingivalis ATCC 33277]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JTC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JTC 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]] 2.39&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C8O:2-(2-azanylethylamino)-5-nitro-benzoic+acid'>C8O</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6jtc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jtc OCA], [https://pdbe.org/6jtc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jtc RCSB], [https://www.ebi.ac.uk/pdbsum/6jtc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jtc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DPP11_PORG3 DPP11_PORG3] Catalyzes the removal of dipeptides from the N-terminus of oligopeptides. Shows a strict specificity for acidic residues (Asp or Glu) in the P1 position, and has a hydrophobic residue preference at the P2 position. Preferentially cleaves the synthetic substrate Leu-Asp-methylcoumaryl-7-amide (Leu-Asp-MCA) as compared to Leu-Glu-MCA. Is involved in amino acid metabolism and bacterial growth of asaccharolytic P.gingivalis, that utilizes amino acids from extracellular proteinaceous nutrients as energy and carbon sources.<ref>PMID:21896480</ref> <ref>PMID:23246913</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Antimicrobial resistance is a global public threat and raises the need for development of new antibiotics with a novel mode of action. The dipeptidyl peptidase 11 from Porphyromonas gingivalis (PgDPP11) belongs to a new class of serine peptidases, family S46. Because S46 peptidases are not found in mammals, these enzymes are attractive targets for novel antibiotics. However, potent and selective inhibitors of these peptidases have not been developed to date. In this study, a high-resolution crystal structure analysis of PgDPP11 using a space-grown crystal enabled us to identify the binding of citrate ion, which could be regarded as a lead fragment mimicking the binding of a substrate peptide with acidic amino acids, in the S1 subsite. The citrate-based pharmacophore was utilized for in silico inhibitor screening. The screening resulted in an active compound SH-5, the first nonpeptidyl inhibitor of S46 peptidases. SH-5 and a lipophilic analog of SH-5 showed a dose-dependent inhibitory effect against the growth of P. gingivalis. The binding mode of SH-5 was confirmed by crystal structure analysis. Thus, these compounds could be lead structures for the development of selective inhibitors of PgDPP11.

Fragment-based discovery of the first nonpeptidyl inhibitor of an S46 family peptidase.,Sakamoto Y, Suzuki Y, Nakamura A, Watanabe Y, Sekiya M, Roppongi S, Kushibiki C, Iizuka I, Tani O, Sakashita H, Inaka K, Tanaka H, Yamada M, Ohta K, Honma N, Shida Y, Ogasawara W, Nakanishi-Matsui M, Nonaka T, Gouda H, Tanaka N Sci Rep. 2019 Sep 19;9(1):13587. doi: 10.1038/s41598-019-49984-3. PMID:31537874<ref>PMID:31537874</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6jtc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Porphyromonas gingivalis ATCC 33277]]
[[Category: Iizuka I]]
[[Category: Kushibiki C]]
[[Category: Nakamura A]]
[[Category: Ogasawara W]]
[[Category: Roppongi S]]
[[Category: Sakamoto Y]]
[[Category: Suzuki Y]]
[[Category: Tanaka N]]