scholarly journals Crystal Structure of the YgfZ Protein from Escherichia coli Suggests a Folate-Dependent Regulatory Role in One-Carbon Metabolism

2004 ◽  
Vol 186 (21) ◽  
pp. 7134-7140 ◽  
Author(s):  
Alexey Teplyakov ◽  
Galina Obmolova ◽  
Elif Sarikaya ◽  
Sadhana Pullalarevu ◽  
Wojciech Krajewski ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Escherichia Coli ◽  
Carbon Metabolism ◽  
Sequence Similarity ◽  
Regulatory Protein ◽  
Domain Architecture ◽  
Protein Molecule ◽  
Large Protein Family ◽  
Glycine Cleavage ◽  
One Carbon Metabolism

ABSTRACT The ygfZ gene product of Escherichia coli represents a large protein family conserved in bacteria to eukaryotes. The members of this family are uncharacterized proteins with marginal sequence similarity to the T-protein (aminomethyltransferase) of the glycine cleavage system. To assist with the functional assignment of the YgfZ family, the crystal structure of the E. coli protein was determined by multiwavelength anomalous diffraction. The protein molecule has a three-domain architecture with a central hydrophobic channel. The structure is very similar to that of bacterial dimethylglycine oxidase, an enzyme of the glycine betaine pathway and a homolog of the T-protein. Based on structural superposition, a folate-binding site was identified in the central channel of YgfZ, and the ability of YgfZ to bind folate derivatives was confirmed experimentally. However, in contrast to dimethylglycine oxidase and T-protein, the YgfZ family lacks amino acid conservation at the folate site, which implies that YgfZ is not an aminomethyltransferase but is likely a folate-dependent regulatory protein involved in one-carbon metabolism.

Control of one-carbon metabolism in a methionine-B12 auxotroph of Escherichia coli

1966 ◽  
Vol 117 (2) ◽  
pp. 405-412 ◽  
Author(s):  
Robert T. Taylor ◽  
Herbert Dickerman ◽  
Herbert Weissbach
Keyword(s):  
Escherichia Coli ◽  
Carbon Metabolism ◽  
One Carbon Metabolism

Ontogeny of hepatic enzymes involved in serine- and folate-dependent one-carbon metabolism in rabbits

2001 ◽  
Vol 280 (5) ◽  
pp. G873-G878 ◽  
Author(s):  
Henry R. Thompson ◽  
Gayle M. Jones ◽  
Michael R. Narkewicz
Keyword(s):  
Carbon Metabolism ◽  
Specific Activity ◽  
Serine Hydroxymethyltransferase ◽  
Central Position ◽  
Fetal Life ◽  
Glycine Cleavage System ◽  
Hepatic Enzymes ◽  
Methenyltetrahydrofolate Synthetase ◽  
Glycine Cleavage ◽  
One Carbon Metabolism

Serine occupies a central position in folate-dependent, one-carbon metabolism through 5,10-methylenetetrahydrofolate (MTHF) and 5-formyltetrahydrofolate (FTHF). We characterized the ontogeny of the specific activity of key enzymes involved in serine, 5,10-MTHF, and 5-FTHF metabolism: methenyltetrahydrofolate synthetase (MTHFS), MTHF reductase (MTHFR), the glycine cleavage system (GCS), methionine synthase (MS), and serine hydroxymethyltransferase (SHMT) in rabbit liver, placenta, brain, and kidney. In liver, MTHFS activity is low in the fetus (0.36 ± 0.07 nmol · min−1 · mg protein−1), peaks at 3 wk (1.48 ± 0.50 nmol · min−1 · mg protein−1), and then decreases to adult levels (1.13 ± 0.32 nmol · min−1 · mg protein−1). MTHFR activity is highest early in gestation (24.9 ± 2.4 nmol · h−1 · mg protein−1) and declines rapidly by birth (4.7 ± 1.3 nmol · h−1 · mg protein−1). MS is highest during fetal life and declines after birth. Cytosolic SHMT activity does not vary during development, but mitochondrial SHMT peaks at 23 days. GCS activity is high in the fetus and the neonate, declining after weaning. In placenta and brain, all activities are low throughout gestation. Cytosolic and mitochondrial SHMT activities are low in kidney and rise after weaning, whereas MTHFS is low throughout development. These data suggest that the liver is the primary site of activity for these enzymes. Throughout development, there are multiple potential sources for production of 5,10-MTHF, but early in gestation high MTHFR activity and low MTHFS activity could reduce 5,10-MTHF availability.

scholarly journals A Novel Two-domain Architecture Within the Amino Acid Kinase Enzyme Family Revealed by the Crystal Structure of Escherichia coli Glutamate 5-kinase

2007 ◽  
Vol 367 (5) ◽  
pp. 1431-1446 ◽  
Author(s):  
Clara Marco-Marín ◽  
Fernando Gil-Ortiz ◽  
Isabel Pérez-Arellano ◽  
Javier Cervera ◽  
Ignacio Fita ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Escherichia Coli ◽  
Amino Acid ◽  
Domain Architecture ◽  
Enzyme Family

scholarly journals Deciphering the enigmatic role of the amidotransferase LipL inBacillus subtilislipoic acid utilization

2018 ◽  
Author(s):  
Natalí B. Rasetto ◽  
Antonela Lavatelli ◽  
Natalia Martin ◽  
María Cecilia Mansilla
Keyword(s):  
Carbon Metabolism ◽  
Essential Role ◽  
Glycine Cleavage System ◽  
Growth Defects ◽  
Gram Positive Bacteria ◽  
Glycine Cleavage ◽  
One Carbon Metabolism ◽  
Branched Chain ◽  
Octanoyl Group

AbstractLipoate is an essential cofactor for key enzymes of oxidative and one-carbon metabolism. It is covalently attached to E2 subunits of dehydrogenase (DH) complexes and the GcvH subunit of the glycine cleavage system.Bacillus subtilispossess two protein lipoylation pathways: biosynthesis and scavenging. The former requires octanoylation of GcvH, amidotransfer of the octanoate to E2s, and insertion of sulfur atoms. Lipoate scavenging is mediated by a lipoate ligase (LplJ), that catalizes a classical two-step ATP-dependent reaction. Although these pathways were thought to be redundant, a ΔlipLmutant, unable to transfer the octanoyl group from GcvH to the E2s during lipoate synthesis, showed growth defects in minimal media even when supplemented with this cofactor, despite the presence of a functional LplJ. In this study we demonstrated that LipL is essential to modify E2 subunits of branched chain ketoacid and pyruvate DH during lipoate scavenging. LipL must be functional and it is not forming a complex with LplJ, which suggests that these enzymes might be acting sequentially. We also show that the E2 subunit of oxoglutarate DH is a good donor for LipL amidotransfer reaction. The essential role of LipL during lipoate utilization relies on the strict substrate specificity of LplJ, determined by charge complementarity between the ligase and the lipoylable subunits. LplJ does not recognize E2 subunits without a negatively charged residue in key positions of the target protein, and thus LipL is required to transfer the lipoate to them. This model of lipoate scavenging seems widespread among Gram-positive bacteria.

Genetic Variation: Impact on Folate (and Choline) Bioefficacy

2010 ◽  
Vol 80 (45) ◽  
pp. 319-329 ◽  
Author(s):  
Allyson A. West ◽  
Marie A. Caudill
Keyword(s):  
Carbon Metabolism ◽  
Genetic Variants ◽  
Plasma Homocysteine ◽  
Water Soluble ◽  
Gene Interactions ◽  
Dietary Folate ◽  
Methyl Donors ◽  
Common Genetic Variants ◽  
One Carbon Metabolism ◽  
The Impact

Folate and choline are water-soluble micronutrients that serve as methyl donors in the conversion of homocysteine to methionine. Inadequacy of these nutrients can disturb one-carbon metabolism as evidenced by alterations in circulating folate and/or plasma homocysteine. Among common genetic variants that reside in genes regulating folate absorptive and metabolic processes, homozygosity for the MTHFR 677C > T variant has consistently been shown to have robust effects on status markers. This paper will review the impact of genetic variants in folate-metabolizing genes on folate and choline bioefficacy. Nutrient-gene and gene-gene interactions will be considered along with the need to account for these genetic variants when updating dietary folate and choline recommendations.

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