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Flexibility, activity and structure correlations in the dipeptidyl peptidase III family, (FlAcS, ID:7235)

Principal investigator

Category
Projekti Hrvatske zaklade za znanost
Finance value
209.000,00
HRK
Start date
Jul 1st 2014
End date
Jun 30th 2017
Status
Done
Flexibility, activity and structure correlations in the dipeptidyl peptidase III family,  (FlAcS, ID:7235)

human DPP III

Within the project frame we intend to investigate diversity in evolutionary conserved metallopeptidase family M49 (DPP III family) through characterization of catalytic, structural and dynamical properties of its members. The project would encompass five dipeptidyl peptidases III (DPP III): human, yeast, two bacterial orthologs, from thermophileCaldithrix abyssiand oral pathogenPorphyromonas gingivalis, and a DPP III from plantPhyscomitrella patens. The DPP III cleaves dipeptides from the N-terminus of many oligopeptides and contributes to the intracellular protein metabolism as well as to endogenous defense against oxidative stress. Human DPP III (h.DPP III) is also related to pathological processes of cataractogenesis, tumor growth and influenza virus infection. The project research should elucidate whether the large flexibility determined for h.DPP III is conserved within DPP IIIs, and how it correlates with the protein function. It would reveal submolecular details important for substrate stabilization and, in the case of h.DPP III, the enzymatic mechanism. Elucidation of the key interactions between h.DPP III and Keap1 protein (Nrf2-Keap1 signalling pathway is major regulator of cytoprotective responses to oxidative and electrophilic stress), and possible correlation of DPP III flexibility with the complex stability, should aid in clarification of its cellular roles. Plant DPP III, differently from DPP IIIs in other organisms possesses a NUDIX box. The project should elucidate its potential dual activity (peptidase and NUDIX). Study of DPP III from thermophile should improve our knowledge on thermophile proteins, potentially useful in biotechnology. In order to fulfill the outlined goals a finely tuned multidisciplinary approach would be used in which molecular biology, biochemistry and mass spectrometry methods would be complemented with bioinformatics, multiscale molecular modelling (coarse-grained/all-atom MD, QM/MM) and macromolecular crystallography

Other associates

Branka Bilić, dr.sc.

Professional advisor
Interni broj:
1358
1258

Nina Jajčanin Jozić

N

J

Interni broj:
1205
1292

Zrinka Karačić, dr.sc.

Postdoctoral researcher
Interni broj:
1303
1205

Borislav Kovačević, dr.sc.

Head of division
Tel:
+385 1 457 1385
Interni broj:
1502

Mihaela Matovina, dr.sc.

Research associate
Tel:
+385 1 457 1223
Interni broj:
1292
1205

Saša Kazazić, dr.sc.

Senior research associate
Tel:
+385 1 456 1077
Interni broj:
1258
1315

Igor Sabljić, dr.sc.

Senior professional associate
Tel:
+385 1 456 1025
Interni broj:
1335

Antonija Tomić, dr.sc.

Research associate
Tel:
+385 1 457 1251
Interni broj:
1265

Marko Tomin, dr.sc.

M

T

Tel:
+385 1 456 1025
Interni broj:
1335

Marija Kozlović

M

K

Interni broj:
1205
1303

Dejan Agić

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