De novo purine nucleotide biosynthesis: cloning, sequencing and expression of a chicken PurH cDNA encoding 5-aminoimidazole-4-carboxamide-ribonucleotide transformylase-IMP cyclohydrolase

Ni, Liuying; Guan, Kun‐Liang; Zalkin, Howard; Dixon, Jack E.

doi:10.1016/0378-1119(91)90199-l

Cited by 39 publications

(23 citation statements)

References 26 publications

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“…The most likely explanation of this result is that enzymes of both pyrimidine and purine biosynthesis are K ϩ iondependent, including carbamoyl phosphate synthetase (the first enzyme of pyrimidine biosynthesis) (19) and AICAR (5-aminoimidazole-4-carboxamide 1-␤-D-ribofuranoside) transformylase-IMP cyclohydrolase, the last enzyme complex of purine biosynthesis (33), which is very likely to require K ϩ ions. This latter conclusion is based on the finding of an essential bound K ϩ ion in the crystal structure of avian AICAR transformylase-IMP cyclohydrolase (9) and the finding that the B. subtilis gene for this enzyme encodes a highly conserved K ϩ ion binding sequence (22). It is notable that all of the pyr and pur mutants obtained here still required K ϩ -ion supplementation for complete surface colonization.…”

Section: Discussionmentioning

confidence: 63%

Genetic Requirements for Potassium Ion-Dependent Colony Spreading inBacillus subtilis

et al. 2005

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Undomesticated strains of Bacillus subtilis exhibit extensive colony spreading on certain soft agarose media: first the formation of dendritic clusters of cells, followed by spreading (pellicle-like) growth to cover the entire surface. These phases of colonization are dependent on the level of potassium ion (K ؉ ) but independent of flagella, as verified with a mutant with a hag gene replacement; this latter finding highlights the importance of sliding motility in colony spreading. Exploring the K ؉ requirement, directed mutagenesis of the higheraffinity K ؉ transporter KtrAB, but not the lower-affinity transporter KtrCD, was found to inhibit surface colonization unless sufficient KCl was added. To identify other genes involved in K ؉ -dependent colony spreading, transposon insertion mutants in wild-type strain 3610 were screened. Disruption of genes for pyrimidine (pyrB) or purine (purD, purF, purH, purL, purM) biosynthetic pathways abolished the K ؉ -dependent spreading phase. Consistent with a requirement for functional nucleic acid biosynthesis, disruption of purine synthesis with the folic acid antagonist sulfamethoxazole also inhibited spreading. Other transposon insertions disrupted acetoin biosynthesis (the alsS gene), acidifying the growth medium, glutamine synthetase (the glnA gene), and two surfactin biosynthetic genes (srfAA, srfAB). This work identified four classes of surface colonization mutants with defective (i) potassium transport, (ii) surfactin formation, (iii) growth rate or yield, or (iv) pH control. Overall, the ability of B. subtilis to colonize surfaces by spreading is highly dependent on balanced nucleotide biosynthesis and nutrient assimilation, which require sufficient K ؉ ions, as well as growth conditions that promote sliding motility.

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Section: Discussionmentioning

confidence: 63%

Genetic Requirements for Potassium Ion-Dependent Colony Spreading inBacillus subtilis

et al. 2005

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“…The strict conservation of these amino acid residues in MTF and the very strong homology in this region among MTF, the glycinamide ribonucleotide formyltransferases, and amino imidazole carboxamide ribonucleotide formyltransferases (46,47) from a number of sources suggest that these amino acids also play a similar catalytic role in MTF. If, as stated above, Lys 207 is at or near the active site of the MTF, it might be close to amino acids 109, 111, and 147 in the three-dimensional structure.…”

Section: Lysmentioning

confidence: 99%

Lysine 207 as the Site of Cross-linking between the 3′-End of Escherichia coli Initiator tRNA and Methionyl-tRNA Formyltransferase

Gite

RajBhandary

1997

Journal of Biological Chemistry

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The specific formylation of initiator methionyl-tRNA by methionyl-tRNA formyltransferase (MTF) is important for initiation of protein synthesis in Escherichia coli. In attempts to identify regions of MTF that come close to the 3-end of the tRNA, we oxidized 32 P-3-endlabeled E. coli initiator methionine tRNA with sodium metaperiodate and cross-linked it to MTF. The crosslinked MTF was separated from uncross-linked MTF by DEAE-cellulose chromatography, and the tRNA in the cross-linked MTF was hydrolyzed with nuclease P1 and RNase T1, leaving behind an oxidized fragment of From assembly and packaging of RNA viruses (1) to mRNA localization during development (2), the specific recognition of RNAs by proteins plays an important role in many biological processes. Examples of these biological processes include RNA processing, RNA splicing, RNA transport, ribosome assembly, translation, and translational regulation (3). As molecules that interact with a variety of different proteins, tRNAs provide an excellent system for studying the molecular basis of specificity in recognition of RNAs by different proteins (4).We are studying the specific recognition of Escherichia coli initiator methionyl-tRNA (Met-tRNA), 1 during its formylation to formylmethionyl-tRNA by the enzyme methionyl-tRNA formyltransferase (MTF, EC 2.1.2.9; 10-formyltetrahydrofolate:L-methionyl-tRNA N-formyltransferase). Formylation of initiator Met-tRNA is important for initiation of protein synthesis in eubacteria and in eukaryotic organelles such as mitochondria and chloroplasts (5-9). In E. coli, formylation provides a positive determinant for allowing the initiation factor IF2 to select the initiator tRNA from other tRNAs (10, 11) and a second negative determinant for blocking the binding of elongation factor EF-Tu to the initiator tRNA (12-14). The formylation reaction is highly specific; the enzyme formylates the initiator Met-tRNA but not the elongator Met-tRNA or any other aminoacyl-tRNA (15). Previous studies have shown that most of the determinants on the initiator tRNA important for its formylation by MTF are clustered in the acceptor stem (16 -19) (Fig. 1). However, although the protein sequence of MTF is known (20), little is known about the amino acid residues in MTF that are important for this recognition and the molecular basis of the specificity in recognition.As a first step in identifying regions of MTF that come close to the acceptor stem of the tRNA, we have cross-linked periodate-oxidized tRNA to MTF and have analyzed the site(s) of cross-linking. We show that Lys 207 in the sequence KLSKE (207-211) of MTF is the site of cross-link to the 3Ј terminus of the tRNA.2 The cross-linking of periodate-oxidized E. coli tRNA fMet to MTF has been studied before by Blanquet and co-workers (21). However, the sites of cross-linking were not analyzed in the previous work. MATERIALS AND METHODSChemicals, Enzymes, and Radioisotopes-Sodium metaperiodate, folinic acid, carboxypeptidase Y (sequencing grade), and methionine were obtained from Sigma. Sod...

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“…The AMPK-activating property of AICAR (via elevation of cellular ZMP) has been used to demonstrate the therapeutic potential for a molecular activator of AMPK, but the short half-life of intravenously administered AICAR, and the resulting rise in levels of blood lactic acid and uric acid, make it unsuitable for direct use as a therapeutic agent (Goodyear, 2008;Karagounis and Hawley, 2009). ZMP is also a cellular metabolite, produced in histidine biosynthesis and de novo purine biosynthesis, but ZMP is only utilized in cells by aminoimidazole carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase (ATIC), a bifunctional 64-kDa enzyme that catalyzes the last two steps of de novo purine biosynthesis (Ni et al, 1991). AMPK activation by exogenous ZMP (administered as the cellpermeable riboside AICAR) suggests a similar function for the endogenous metabolite, indicating the possibility of regulatory crosstalk (via ZMP) between the de novo purine biosynthesis, histidine biosynthesis, and AMPK pathways (Rebora et al, 2005;Corton et al, 1994;Xiao et al, 2007Xiao et al, , 2011.…”

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confidence: 99%

AMPK Activation via Modulation of De Novo Purine Biosynthesis with an Inhibitor of ATIC Homodimerization

Asby

Cuda

Beyaert

et al. 2015

Chemistry & Biology

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5-Aminoimidazole-4-carboxamide ribonucleotide (known as ZMP) is a metabolite produced in de novo purine biosynthesis and histidine biosynthesis, but only utilized in the cell by a homodimeric bifunctional enzyme (called ATIC) that catalyzes the last two steps of de novo purine biosynthesis. ZMP is known to act as an allosteric activator of the cellular energy sensor adenosine monophosphate-activated protein kinase (AMPK), when exogenously administered as the corresponding cell-permeable ribonucleoside. Here, we demonstrate that endogenous ZMP, produced by the aforementioned metabolic pathways, is also capable of activating AMPK. Using an inhibitor of ATIC homodimerization to block the ninth step of de novo purine biosynthesis, we demonstrate that the subsequent increase in endogenous ZMP activates AMPK and its downstream signaling pathways. We go on to illustrate the viability of using this approach to AMPK activation as a therapeutic strategy with an in vivo mouse model for metabolic disorders.

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De novo purine nucleotide biosynthesis: cloning, sequencing and expression of a chicken PurH cDNA encoding 5-aminoimidazole-4-carboxamide-ribonucleotide transformylase-IMP cyclohydrolase

Cited by 39 publications

References 26 publications

Genetic Requirements for Potassium Ion-Dependent Colony Spreading inBacillus subtilis

Genetic Requirements for Potassium Ion-Dependent Colony Spreading inBacillus subtilis

Lysine 207 as the Site of Cross-linking between the 3′-End of Escherichia coli Initiator tRNA and Methionyl-tRNA Formyltransferase

AMPK Activation via Modulation of De Novo Purine Biosynthesis with an Inhibitor of ATIC Homodimerization

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