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@ARTICLE{Sorci:642756,
author = {Sorci, Leonardo and Cianci, Michele and Fortunato, Carlo
and Gasparrini, Massimiliano and Raffaelli, Nadia},
title = {{A}rabidopsis thaliana nicotinate mononucleotide
adenylyltransferase: unveiling the molecular determinants
and evolutionary origin of nicotinic acid mononucleotide
recognition},
journal = {International journal of biological macromolecules},
volume = {331},
issn = {0141-8130},
address = {New York, NY [u.a.]},
publisher = {Elsevier},
reportid = {PUBDB-2025-05605},
pages = {148370},
year = {2025},
abstract = {The pyridine nucleotide adenylyltransferase (PNAT) enzyme
family is crucial for the synthesis of NAD, a pivotal
cofactor in cellular metabolism. PNATs catalyze the transfer
of an AMP moiety from ATP to either nicotinate
mononucleotide (NaMN), forming nicotinate adenine
dinucleotide, the immediate precursor to NAD, or to
nicotinamide mononucleotide (NMN), directly yielding NAD.
This enzyme family exhibits modular substrate specificity,
comprising strictly NaMN-selective (bacterial NadD),
NMN-selective (bacterial NadR and NadM), or bifunctional
(mammalian PNAT and archaeal NadM). While Arabidopsis
thaliana PNAT has been ambiguously annotated as
bifunctional, our detailed kinetic analysis definitively
establishes its strict NaMN preference, analogous to
bacterial NadD. By integrating bioinformatics and X-ray
crystallography of the enzyme in its apo and NaMN-bound
forms, we elucidate the structural basis for NaMN
selectivity, which differs from bacterial NadD. In plants, a
positively charged residue (Arg106 in A. thaliana NaMN
adenylyltransferase, NaMNAT) ensures NaMN specificity by
counteracting the negative charge of the nicotinate moiety.
Site-directed mutagenesis confirms the essential role of
Arg106 in NaMN recognition and catalysis. Our findings
support the extension of this functional assignment across
Archaeoplastida. Furthermore, phylogenetic analysis reveals
the complex and intertwined evolution of bacterial and plant
NaMNATs, shaped by ancient gene transfers from
cyanobacteria.},
cin = {EMBL-User},
ddc = {570},
cid = {I:(DE-H253)EMBL-User-20120814},
pnm = {6G3 - PETRA III (DESY) (POF4-6G3)},
pid = {G:(DE-HGF)POF4-6G3},
experiment = {EXP:(DE-H253)P-P13-20150101},
typ = {PUB:(DE-HGF)16},
doi = {10.1016/j.ijbiomac.2025.148370},
url = {https://bib-pubdb1.desy.de/record/642756},
}