Comparison of human glutamate carboxypeptidases II and III reveals their divergent substrate specificities

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00468320" target="_blank" >RIV/61388963:_____/16:00468320 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/16:10324109

Result on the web

<a href="http://dx.doi.org/10.1111/febs.13761" target="_blank" >http://dx.doi.org/10.1111/febs.13761</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/febs.13761" target="_blank" >10.1111/febs.13761</a>

Result language

angličtina

Original language name

Comparison of human glutamate carboxypeptidases II and III reveals their divergent substrate specificities

Original language description

Glutamate carboxypeptidase III (GCPIII) is best known as a homologue of glutamate carboxypeptidase II [GCPII; also known as prostate-specific membrane antigen (PSMA)], a protease involved in neurological disorders and overexpressed in a number of solid cancers. However, mouse GCPIII was recently shown to cleave beta-citrylglutamate (BCG), suggesting that these two closely related enzymes have distinct functions. To develop a tool to dissect, evaluate and quantify the activities of human GCPII and GCPIII, we analysed the catalytic efficiencies of these enzymes towards three physiological substrates. We observed a high efficiency of BCG cleavage by GCPIII but not GCPII. We also identified a strong modulation of GCPIII enzymatic activity by divalent cations, while we did not observe this effect for GCPII. Additionally, we used X-ray crystallography and computational modelling (quantum and molecular mechanical calculations) to describe the mechanism of BCG binding to the active sites of GCPII and GCPIII, respectively. Finally, we took advantage of the substantial differences in the enzymatic efficiencies of GCPII and GCPIII towards their substrates, using enzymatic assays for specific detection of these proteins in human tissues. Our findings suggest that GCPIII may not act merely as a complementary enzyme to GCPII, and it more likely possesses a specific physiological function related to BCG metabolism in the human body.

Czech name

—

Czech description

—

Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

—

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

FEBS Journal

ISSN

1742-464X

e-ISSN

—

Volume of the periodical

283

Issue of the periodical within the volume

13

Country of publishing house

GB - UNITED KINGDOM

Number of pages

18

Pages from-to

2528-2545

UT code for WoS article

000383601600010

EID of the result in the Scopus database

2-s2.0-84978066573