5jwf

Crystal structure of Porphyromonas gingivalis DPP11Crystal structure of Porphyromonas gingivalis DPP11

Structural highlights

5jwf is a 2 chain structure with sequence from Porphyromonas gingivalis. 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

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.^[1] ^[2]

Publication Abstract from PubMed

Porphyromonas gingivalis and Porphyromonas endodontalis are important bacteria related to periodontitis, the most common chronic inflammatory disease in humans worldwide. Its comorbidity with systemic diseases, such as type 2 diabetes, oral cancers and cardiovascular diseases, continues to generate considerable interest. Surprisingly, these two microorganisms do not ferment carbohydrates; rather they use proteinaceous substrates as carbon and energy sources. However, the underlying biochemical mechanisms of their energy metabolism remain unknown. Here, we show that dipeptidyl peptidase 11 (DPP11), a central metabolic enzyme in these bacteria, undergoes a conformational change upon peptide binding to distinguish substrates from end products. It binds substrates through an entropy-driven process and end products in an enthalpy-driven fashion. We show that increase in protein conformational entropy is the main-driving force for substrate binding via the unfolding of specific regions of the enzyme ("entropy reservoirs"). The relationship between our structural and thermodynamics data yields a distinct model for protein-protein interactions where protein conformational entropy modulates the binding free-energy. Further, our findings provide a framework for the structure-based design of specific DPP11 inhibitors.

Bacterial protease uses distinct thermodynamic signatures for substrate recognition.,Bezerra GA, Ohara-Nemoto Y, Cornaciu I, Fedosyuk S, Hoffmann G, Round A, Marquez JA, Nemoto TK, Djinovic-Carugo K Sci Rep. 2017 Jun 6;7(1):2848. doi: 10.1038/s41598-017-03220-y. PMID:28588213^[3]

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

References

↑ Ohara-Nemoto Y, Shimoyama Y, Kimura S, Kon A, Haraga H, Ono T, Nemoto TK. Asp- and Glu-specific novel dipeptidyl peptidase 11 of Porphyromonas gingivalis ensures utilization of proteinaceous energy sources. J Biol Chem. 2011 Nov 4;286(44):38115-27. doi: 10.1074/jbc.M111.278572. Epub 2011, Sep 6. PMID:21896480 doi:http://dx.doi.org/10.1074/jbc.M111.278572
↑ Rouf SM, Ohara-Nemoto Y, Hoshino T, Fujiwara T, Ono T, Nemoto TK. Discrimination based on Gly and Arg/Ser at position 673 between dipeptidyl-peptidase (DPP) 7 and DPP11, widely distributed DPPs in pathogenic and environmental gram-negative bacteria. Biochimie. 2013 Apr;95(4):824-32. doi: 10.1016/j.biochi.2012.11.019. Epub 2012, Dec 12. PMID:23246913 doi:http://dx.doi.org/10.1016/j.biochi.2012.11.019
↑ Bezerra GA, Ohara-Nemoto Y, Cornaciu I, Fedosyuk S, Hoffmann G, Round A, Marquez JA, Nemoto TK, Djinovic-Carugo K. Bacterial protease uses distinct thermodynamic signatures for substrate recognition. Sci Rep. 2017 Jun 6;7(1):2848. doi: 10.1038/s41598-017-03220-y. PMID:28588213 doi:http://dx.doi.org/10.1038/s41598-017-03220-y

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Ohara-Nemoto Y, Shimoyama Y, Kimura S, Kon A, Haraga H, Ono T, Nemoto TK. Asp- and Glu-specific novel dipeptidyl peptidase 11 of Porphyromonas gingivalis ensures utilization of proteinaceous energy sources. J Biol Chem. 2011 Nov 4;286(44):38115-27. doi: 10.1074/jbc.M111.278572. Epub 2011, Sep 6. PMID:21896480 doi:http://dx.doi.org/10.1074/jbc.M111.278572

[2] Rouf SM, Ohara-Nemoto Y, Hoshino T, Fujiwara T, Ono T, Nemoto TK. Discrimination based on Gly and Arg/Ser at position 673 between dipeptidyl-peptidase (DPP) 7 and DPP11, widely distributed DPPs in pathogenic and environmental gram-negative bacteria. Biochimie. 2013 Apr;95(4):824-32. doi: 10.1016/j.biochi.2012.11.019. Epub 2012, Dec 12. PMID:23246913 doi:http://dx.doi.org/10.1016/j.biochi.2012.11.019

[3] Bezerra GA, Ohara-Nemoto Y, Cornaciu I, Fedosyuk S, Hoffmann G, Round A, Marquez JA, Nemoto TK, Djinovic-Carugo K. Bacterial protease uses distinct thermodynamic signatures for substrate recognition. Sci Rep. 2017 Jun 6;7(1):2848. doi: 10.1038/s41598-017-03220-y. PMID:28588213 doi:http://dx.doi.org/10.1038/s41598-017-03220-y

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