Structural basis of prostate-specific membrane antigen recognition by the A9g RNA aptamer
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F20%3A00541410" target="_blank" >RIV/86652036:_____/20:00541410 - isvavai.cz</a>
Alternative codes found
RIV/68407700:21340/20:00343689
Result on the web
<a href="https://academic.oup.com/nar/article/48/19/11130/5856120" target="_blank" >https://academic.oup.com/nar/article/48/19/11130/5856120</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/nar/gkaa494" target="_blank" >10.1093/nar/gkaa494</a>
Alternative languages
Result language
angličtina
Original language name
Structural basis of prostate-specific membrane antigen recognition by the A9g RNA aptamer
Original language description
Prostate-specific membrane antigen (PSMA) is a well-characterized tumor marker associated with prostate cancer and neovasculature of most solid tumors. PSMA-specific ligands are thus being developed to deliver imaging or therapeutic agents to cancer cells. Here, we report on a crystal structure of human PSMA in complex with A9g, a 43-bp PSMA-specific RNA aptamer, that was determined to the 2.2 angstrom resolution limit. The analysis of the PSMA/aptamer interface allows for identification of key interactions critical for nanomolar binding affinity and high selectivity of A9g for human PSMA. Combined with in silico modeling, site-directed mutagenesis, inhibition experiments and cell-based assays, the structure also provides an insight into structural changes of the aptamer and PSMA upon complex formation, mechanistic explanation for inhibition of the PSMA enzymatic activity by A9g as well as its ligand-selective competition with small molecules targeting the internal pocket of the enzyme. Additionally, comparison with published protein-RNA aptamer structures pointed toward more general features governing protein-aptamer interactions. Finally, our findings can be exploited for the structure-assisted design of future A9g-based derivatives with improved binding and stability characteristics.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
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
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nucleic Acids Research
ISSN
0305-1048
e-ISSN
—
Volume of the periodical
48
Issue of the periodical within the volume
19
Country of publishing house
GB - UNITED KINGDOM
Number of pages
16
Pages from-to
11130-11145
UT code for WoS article
000606018400042
EID of the result in the Scopus database
2-s2.0-85089597828