Role of aspartic acid residues D87 and D89 in APS kinase domain of human 3 '-phosphoadenosine 5 '-phosphosulfate synthase 1 and 2b: A commonality with phosphatases/kinases
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11320%2F21%3A10438876" target="_blank" >RIV/00216208:11320/21:10438876 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=h6T4udGaIG" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=h6T4udGaIG</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bbrep.2021.101155" target="_blank" >10.1016/j.bbrep.2021.101155</a>
Alternative languages
Result language
angličtina
Original language name
Role of aspartic acid residues D87 and D89 in APS kinase domain of human 3 '-phosphoadenosine 5 '-phosphosulfate synthase 1 and 2b: A commonality with phosphatases/kinases
Original language description
3'-phosphoadenosine 5'-phosphosulfate (PAPS) is synthesized in two steps by PAPS synthase (PAPSS). PAPSS is comprised of ATP sulfurylase (ATPS) and APS kinase (APSK) domain activities. ATPS combines inorganic sulfate with a-phosphoryl of ATP to form adenosine 5'-phosphosulfate (APS) and PPi. In the second step APS is phosphorylated at 3'-OH using another mole of ATP to form PAPS and ADP catalyzed by APSK. The transfer of gamma-phosphoryl from ATP onto 3'-OH requires Mg-2(+) and purported to involve residues D(87)GD(89)N. We report that mutation of either aspartic residue to alanine completely abolishes APSK activity in PAPS formation. PAPSS is an, unique enzyme that binds to four different nucleotides: ATP and APS on both ATPS and APSK domains and ADP and PAPS exclusively on the APSK domain. The thermodynamic binding and the catalytic interplay must be very tightly controlled to form the end-product PAPS in the forward direction. Though APS binds to ATPS and APSK, in ATPS domain, the APS is a product and for APSK it is a substrate. DGDN motif is absent in ATPS and present in APSK. Mutation of D-87 and D-89 did not hamper ATPS activity however abolished APSK activity severely. Thus, D(87)GD(89)N region is required for stabilization of Mg2+-ATP, in the process of splitting the 7-phosphoryl from ATP and transfer of 7-phosphoryl onto 3'-OH of APS to form PAPS a process that cannot be achieved by ATPS domain. In addition, gamma P-32-ATP, trapped phosphoryl enzyme intermediate more with PAPSS2 than with PAPSS1. This suggests inherent active site residues could control novel catalytic differences. Molecular docking studies of hPAPSS1 with ATP + Mg2+ and APS of wild type and mutants supports the experimental results.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10301 - Atomic, molecular and chemical physics (physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect)
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biochemistry and Biophysics Reports [online]
ISSN
2405-5808
e-ISSN
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Volume of the periodical
28
Issue of the periodical within the volume
5
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
9
Pages from-to
101155
UT code for WoS article
000732710600008
EID of the result in the Scopus database
2-s2.0-85122798048