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Crystal structure of dipeptidyl peptidase III from the human gut symbiont Bacteroides thetaiotaomicron

Sabljić, Igor; Meštrović Radan, Nevenka; Vukelić, Bojana; Macheroux, Peter; Gruber, Karl; Luić, Marija; Abramić, Marija (2017) Crystal structure of dipeptidyl peptidase III from the human gut symbiont Bacteroides thetaiotaomicron. PLoS One, 12 (11). ISSN 1932-6203

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Bacteroides thetaiotaomicron is a dominant member of the human intestinal microbiome. The genome of this anaerobe encodes more than 100 proteolytic enzymes, the majority of which have not been characterized. In the present study, we have produced and purified recombinant dipeptidyl peptidase III (DPP III) from B. thetaiotaomicron for the purposes of biochemical and structural investigations. DPP III is a cytosolic zinc-metallopeptidase of the M49 family, involved in protein metabolism. The biochemical results for B. thetaiotaomicron DPP III from our research showed both some similarities to, as well as certain differences from, previously characterised yeast and human DPP III. The 3D-structure of B. thetaiotaomicron DPP III was determined by X-ray crystallography and revealed a two-domain protein. The ligand-free structure (refined to 2.4 Å) was in the open conformation, while in the presence of the hydroxamate inhibitor Tyr-Phe-NHOH, the closed form (refined to 3.3 Å) was observed. Compared to the closed form, the two domains of the open form are rotated away from each other by about 28 degrees. A comparison of the crystal structure of B. thetaiotaomicron DPP III with that of the human and yeast enzymes revealed a similar overall fold. However, a significant difference with functional implications was discovered in the upper domain, farther away from the catalytic centre. In addition, our data indicate that large protein flexibility might be conserved in the M49 family.

Item Type: Article
Uncontrolled Keywords: dipeptidyl peptidase III ; Bacteroides thetaiotaomicron ; crystal structure ; peptidase family M49 ; zinc-dependent metallopeptidases ; DPP III
Subjects: NATURAL SCIENCES > Chemistry
Divisions: Division of Molecular Biology
Division of Organic Chemistry and Biochemistry
Division of Physical Chemistry
Project titleProject leaderProject codeProject type
Enhancement of the Innovation Potential in SEE through new Molecular Solutions in Research and Development-INNOMOLOliver Vugrek316289EK
Molekularna enzimologija i proteinske interakcije hidrolaza-Marija Abramić098-1191344-2938MZOS
Depositing User: Igor Sabljić
Date Deposited: 16 Jan 2018 15:05
DOI: 10.1371/journal.pone.0187295

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