Influence of dipeptidyl peptidase IV on enzymatic properties of adenosine deaminase

• Authors: Svetlana Sharoyan , Alvard Antonyan , Sona Mardanyan , Giulio Lupidi , Gloria Cristalli
• Languages of publication: EN

Abstracts

EN

The importance of ADA (adenosine deaminase) in the immune system and the role of its interaction with an ADA-binding cell membrane protein dipeptidyl peptidase IV (DPPIV), identical to the activated immune cell antigen, CD26, has attracted the interest of researchers for many years. To investigate the specific properties in the structure - function relationship of the ADA/DPPIV-CD26 complex, its soluble form, identical to large ADA (LADA), was isolated from human blood serum, human pleural fluid and bovine kidney cortex. The kinetic constants (Km and Vmax) of LADA and of small ADA (SADA), purified from bovine lung and spleen, were compared using adenosine (Ado) and 2'-deoxyadenosine (2'-dAdo) as substrates. The Michaelis constant, Km, evidences a higher affinity of both substrates (in particular of more toxic 2'-dAdo) for LADA and proves the modulation of toxic nucleoside neutralization in the extracellular medium due to complex formation between ADA and DPPIV-CD26. The values of Vmax are significantly higher for SADA, but the efficiency, Vmax /Km, in LADA-catalyzed 2'-dAdo deamination is higher than that in Ado deamination. The interaction of all enzyme preparations with derivatives of adenosine and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) was studied. 1-DeazaEHNA and 3-deazaEHNA demonstrate stronger inhibiting activity towards LADA, the DPPIV-CD26-bound form of ADA. The observed differences between the properties of the two ADA isoforms may be considered as a consequence of SADA binding with DPPIV-CD26. Both SADA and LADA indicated a similar pH-profile of adenosine deamination reaction with the optimum at pHs 6.5 - 7.5, while the pH-profile of dipeptidyl peptidase activity of the ADA/DPPIV-CD26 complex appeared in a more alkaline region.

Keywords

EN

protein-protein interaction; large and small adenosine deaminases; CD26-dipeptidyl peptidase IV; enzyme-substrate and enzyme-inhibitor interactions

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2006
• Volume: 53
• Issue: 3
• Pages: 539-546

Dates

published

2006

received

2006-01-18

revised

2006-05-08

accepted

2006-05-18

(unknown)

2006-08-21

Contributors

author

Svetlana Sharoyan

• H.Ch. Buniatyan Institute of Biochemistry, Yerevan, Armenia

author

Alvard Antonyan

• H.Ch. Buniatyan Institute of Biochemistry, Yerevan, Armenia

author

Sona Mardanyan

• H.Ch. Buniatyan Institute of Biochemistry, Yerevan, Armenia

author

Giulio Lupidi

• Department of Biology M.C.A. Sciences, University of Camerino, Camerino, Italy

author

Gloria Cristalli

• Department of Chemical Sciences, University of Camerino, Camerino, Italy

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