Structural and Functional Characterization of Human NAD Kinase

Lerner, Felicitas; Niere, Marc; Ludwig, Antje; Ziegler, Mathias

doi:10.1006/bbrc.2001.5735

Cited by 160 publications

(178 citation statements)

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“…Consequently, we set out to clone and characterize NADKs from the model plant Arabidopsis. Using sequences of the recently cloned human (Lerner et al, 2001), yeast (Kawai et al, 2001b), and bacteria (Kawai et al, 2001b) NADKs, database searches identified two putative NADKs in the Arabidopsis genome. We have named these genes NADK1 and NADK2, and they correspond to loci At3g21070 and At1g21640, respectively.…”

Section: Isolation Of Cdnas and Sequence Analysesmentioning

confidence: 99%

“…NADKs have been found in all organisms examined to date, suggesting a fundamental role for the enzyme (McGuinness and Butler, 1985;Zielinski, 1998;Kawai et al, 2001aKawai et al, , 2001bLerner et al, 2001). While the importance of the pyridine nucleotides NAD(H) and NADP(H) in energy metabolism and reductive biosynthesis is well established, the role of NADK itself remains unclear.…”

mentioning

confidence: 99%

“…While the importance of the pyridine nucleotides NAD(H) and NADP(H) in energy metabolism and reductive biosynthesis is well established, the role of NADK itself remains unclear. Furthermore, while the enzyme has been studied for decades in various organisms, it was only recently that cDNAs encoding NADKs were cloned from bacteria (Kawai et al, 2000(Kawai et al, , 2001a, yeast (Kawai et al, 2001b), and human (Lerner et al, 2001) sources. Until this study, a cDNA encoding a plant NADK had not been isolated, and the lack of molecular tools has hindered research progress on the roles of NADKs in plants.…”

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confidence: 99%

“…However, it remains unclear whether this modulation is direct or indirect (e.g. via CaM-dependent kinase), and recent studies with a human recombinant NADK did not reveal any effect of CaM on in vitro NADK activity (Lerner et al, 2001). Conversely, the modulation of plant NADK by CaM is well established (for review, see Zielinski, 1998).…”

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Cloning and Characterization of Two NAD Kinases from Arabidopsis. Identification of a Calmodulin Binding Isoform

et al. 2004

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NAD kinase (NADK; ATP:NAD 2#-phosphotransferase, EC 2.7.1.23), an enzyme found in both prokaryotes and eukaryotes, generates the important pyridine nucleotide NADP from substrates ATP and NAD. The role of NADKs in plants is poorly understood, and cDNAs encoding plant NADKs have not previously been described to our knowledge. We have cloned two cDNAs from Arabidopsis predicted to encode NADK isoforms, designated NADK1 and NADK2, respectively. Expressed as recombinant proteins in bacteria, both NADK1 and NADK2 were catalytically active, thereby confirming their identity as NADKs. Transcripts for both isoforms were detected in all tissues examined and throughout development. Although the predicted catalytic regions for NADK1 and NADK2 show sequence similarity to NADKs from other organisms, NADK2 possesses a large N-terminal extension that appears to be unique to plants. Using recombinant glutathione-S-transferase fusion proteins and calmodulin (CaM)-affinity chromatography, we delineated a Ca 21 -dependent CaM-binding domain to a 45-residue region within the N-terminal extension of NADK2. Although recombinant NADK2 was not responsive to CaM in vitro, immunoblot analysis suggests that native NADK2 is a CaM-binding protein. In Arabidopsis crude extracts, CaMdependent NADK activity was much greater than CaM-independent activity throughout development, particularly in young seedlings. A native CaM-dependent NADK was partially purified from Arabidopsis seedlings (K m NAD 5 0.20 mM, K m Mg 21 2ATP 5 0.17 mM). The enzyme was fully activated by conserved CaM (S 0.5 5 2.2 nM) in the presence of calcium but displayed differential responsiveness to eight CaM-like Arabidopsis proteins. Possible roles for NADKs in plants are discussed in light of our observations.

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Section: Isolation Of Cdnas and Sequence Analysesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Cloning and Characterization of Two NAD Kinases from Arabidopsis. Identification of a Calmodulin Binding Isoform

et al. 2004

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“…Vainio et al 49 using 35 S UTP-labeled riboprobes on tissue sections of coronal and sagittal sutures dissected from embryonic CD1 mice. Both bright-and dark-field images were taken of hybridized sections.…”

Section: Gene Identificationmentioning

confidence: 99%

Delineation of mechanisms and regions of dosage imbalance in complex rearrangements of 1p36 leads to a putative gene for regulation of cranial suture closure

Gajęcka

Ballif

et al. 2004

Eur J Hum Genet

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Structural chromosome abnormalities have aided in gene identification for over three decades. Delineation of the deletion sizes and rearrangements allows for phenotype/genotype correlations and ultimately assists in gene identification. In this report, we have delineated the precise rearrangements in four subjects with deletions, duplications, and/or triplications of 1p36 and compared the regions of imbalance to two cases recently published. Fluorescence in situ hybridization (FISH) analysis revealed the size, order, and orientation of the duplicated/triplicated segments in each subject. We propose a premeiotic model for the formation of these complex rearrangements in the four newly ascertained subjects, whereby a deleted chromosome 1 undergoes a combination of multiple breakage-fusion-bridge (BFB) cycles and inversions to produce a chromosome arm with a complex rearrangement of deleted, duplicated and triplicated segments. In addition, comparing the six subjects' rearrangements revealed a region of overlap that when triplicated is associated with craniosynostosis and when deleted is associated with large, late-closing anterior fontanels. Within this region are the MMP23A and -B genes. We show MMP23 gene expression at the cranial sutures and we propose that haploinsufficiency results in large, late-closing anterior fontanels and overexpression results in craniosynostosis. These data emphasize the important role of cytogenetics in investigating and uncovering the etiologies of human genetic disease, particularly cytogenetic imbalances that reveal potentially dosage-sensitive genes.

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Emissive Synthetic Cofactors: Enzymatic Interconversions of ^tzA Analogues of ATP, NAD⁺, NADH, NADP⁺, and NADPH

et al. 2017

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As eries of enzymatic transformations,w hich generate visibly emissive isofunctional cofactors based on an isothiazolo [4,3-d]pyrimidine analogue of adenosine ( tz A), was developed. Nicotinamide adenylyl transferase condenses nicotinamide mononucleotide and tz ATP to yield N tz AD + ,w hich can be enzymatically phosphorylated by NAD + kinase and ATPor tz ATP to the corresponding N tz ADP + .The latter can be engaged in NADP-specific coupled enzymatic transformations involving conversion to N tz ADPH by glucose-6-phosphate dehydrogenase and reoxidation to N tz ADP + by glutathione reductase.The N tz ADP + /N tz ADPH cycle can be monitored in real time by fluorescence spectroscopy. Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/anie.201711935. tz A: isothiazolo[4,3-d]pyrimidine analogue of adenosine. Scheme 1. Synthesis of tz ATP.i )POCl 3 ,( MeO) 3 PO, 0 8 8Ct ort, 2h; ii)tributylammonium pyrophosphate, Bu 3 N, 0 8 8Ct ort, 2h,20%. Angewandte Chemie Communications Conflict of interestProfessor Torp rovides consulting services to Tr iLink Biotechnologies.T he terms of the arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies.

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Structural and Functional Characterization of Human NAD Kinase

Cited by 160 publications

References 32 publications

Cloning and Characterization of Two NAD Kinases from Arabidopsis. Identification of a Calmodulin Binding Isoform

Cloning and Characterization of Two NAD Kinases from Arabidopsis. Identification of a Calmodulin Binding Isoform

Delineation of mechanisms and regions of dosage imbalance in complex rearrangements of 1p36 leads to a putative gene for regulation of cranial suture closure

Emissive Synthetic Cofactors: Enzymatic Interconversions of ^tzA Analogues of ATP, NAD⁺, NADH, NADP⁺, and NADPH

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Structural and Functional Characterization of Human NAD Kinase

Cited by 160 publications

References 32 publications

Cloning and Characterization of Two NAD Kinases from Arabidopsis. Identification of a Calmodulin Binding Isoform

Cloning and Characterization of Two NAD Kinases from Arabidopsis. Identification of a Calmodulin Binding Isoform

Delineation of mechanisms and regions of dosage imbalance in complex rearrangements of 1p36 leads to a putative gene for regulation of cranial suture closure

Emissive Synthetic Cofactors: Enzymatic Interconversions of tzA Analogues of ATP, NAD+, NADH, NADP+, and NADPH

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Emissive Synthetic Cofactors: Enzymatic Interconversions of ^tzA Analogues of ATP, NAD⁺, NADH, NADP⁺, and NADPH