Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:6.4.1.1 (pyruvate carboxylase)
1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The complete amino acid sequence of the biotinyl subunit from the enzyme transcarboxylase of Propionibacterium shermanii has been determined from the structures of overlapping tryptic and cyanogen bromide peptides together with sequenator analysis on the whole subunit. The subunit contains 123 amino acid residues. Eleven of nineteen residues in the region of biotin attachment, when compared to pyruvate carboxylase from avian liver (Rylatt, D. B., Keech, D. B., and Wallace, J. C. (1977) Arch. Biochem. Biophys. 183, 113-122), were found to be in identical positions relative to biocytin. There was less homology with acetyl-CoA carboxylase from Escherichia coli (Sutton, M. R., Fall, R. R., Nervi, A. M., Alberts, A. W., Vagelos, P. R., and Bradshaw, R. A. (1977) J. Biol. Chem. 252, 3934-3940), but in all of these biotin enzymes there was an alanylmethionyl-biocytinyl-methionine sequence. The secondary structure of the biotinyl subunit has been estimated using the method of Chou and Fasman (Chou, P. Y., and Fasman, G. D. (1978) Adv. Enzymol. 47, 45-148) and considered in relationship to the role of the biotinyl subunit in the structure and function in transcarboxylase.
...
PMID:Amino acid sequence of the biotinyl subunit from transcarboxylase. 4 Sep 85

Methods were developed for the coupling of biotin to bovine serum albumin and bovine gamma-globulin using a water-soluble carbodimide. The use of [14-C]biotin as a tracer allowed quantitation of the incorporation of biotin into the conjugates: 2.55 mol of biotin was incorporated per mol of gamma-globulin and 7-9 mol of biotin was incorporated per mol of serum albumin in different preparations. These conjugates were highly immunogenic in the rabbit and anti-bodies reactive with the biotinyl group itself could be detected by their ability to precipitate the heterologous biotinated carrier but not the unmodified heterologous carrier. There antisera rapidly inactivated transcarboxylase and pyruvate carboxylase and this inactivation could be blocked by pretreatment of the antisera with biotin or biocytin. Using enzyme inhibition to detect free antibody, the binding constant for biotin was found to be 5.0 x 10- minus 8 M and that for biocytin 3.5 x 10- minus 8 M.
...
PMID:Production of antibodies that bind biotin and inhibit biotin containing enzymes. 4 92

Varieties of pyruvate carboxylase [pyruvate: CO2 ligase (ADP-forming), EC 6.4.1.1] obtained from the livers of several species of vertebrates, including humans, all show the same basic structure. They are composed of large polypeptide chains of molecular weights ranging from 1.2 to 1.3 X 10(5) for the different varieties of the enzyme. The native form of the enzyme appears to be a tetramer with a molecular weight of about 5 X 10(5). In the case of pyruvate carboxylase from chicken liver each polypeptide chain contains a biotin moiety, thus supporting the thesis that the tetramer contains four identical polypeptide chains. Pyruvate carboxylase from yeast appears to be basically similar to those from the vertebrate species and has a tetrameric structure. Each protomer contains a single polypeptide chain with a molecular weitht of 1.25 X 10(5). In contrast, pyruvate carboxylase from two bacterial species, Pseudomonas citronellolis and Axotobacter vinelandii, appears to be a dimer with a molecular weight (2.5 X 10(5)) about half that of the animal and yeast species. As a further difference, each of the protomers of the bacterial enzymes contain two polypeptides of 6.5 and 5.4 X 10(5) molecular weight in case of the Pseudomonas enzyme. The larger of the two polypeptides contains the biotin moiety. The functional units of the bacterial enzyme thus appear to contain two polypeptides while that of the liver and yeast enzymes is made up of a single chain. Neither of these arrangements corresponds with those of other biotin enzymes whose structure has been extensively studied (acetyl-CoA carboxylases from liver or Excherichia coli, and transcarboxylase from Propionibacterium).
...
PMID:Structural properties of pyruvate carboxylases from chicken liver and other sources. 110 79

Veillonella parvula cannot grow with succinate as sole energy source. However, succinate decarboxylation simultaneous with malate or lactate fermentation increased growth yields by 2.4-3.5 g (mol succinate)-1. Malate was fermented stoichiometrically to acetate and propionate whereas lactate fermentation produced more acetate and considerable amounts of H2. Aspartate was utilized only in the presence of succinate as co-substrate. Methylmalonyl-CoA decarboxylase and ATP-dependent pyruvate carboxylase, but not methylmalonyl-CoA:pyruvate transcarboxylase, were detected in cell-free extracts of malate- or lactate-grown cells. The energetic aspects of these fermentation patterns are discussed.
...
PMID:Energy conservation by succinate decarboxylation in Veillonella parvula. 164 32

Biotin-dependent carboxylases require covalently bound biotin for enzymatic activity. The biotin is attached through a lysine residue, which in a number of bacterial, avian, and mammalian carboxylases, is found within the conserved sequence Ala-Met-Lys-Met. We have determined the partial nucleotide sequence of cDNA clones for human propionyl-CoA carboxylase and pyruvate carboxylase. The predicted amino acid sequence of both these proteins contains the conserved tetrapeptide 35 residues from the carboxy terminus. In addition, both proteins contain the tripeptide, Pro-Met-Pro, 26 residues toward the amino terminus from the biotin attachment site. The overall amino acid homology through this region is 43%. Similar findings have been made for the biotin-containing polypeptides of transcarboxylase of Propionibacterium shermanii and acetyl-CoA carboxylase of Escherichia coli (W. L. Maloy, B. U. Bowien, G. K. Zwolinski, K. G. Kumar, and H. G. Wood (1979) J. Biol. Chem. 254, 11615-11622). The implications of this sequence conservation with regard to the function and evolution of biotin-dependent carboxylases is discussed. We propose that the 60 amino acids surrounding the biotin site are bounded by a proline "hinge" and the carboxy terminus has remained conserved as a result of constraints imposed by biotinylation of the enzyme.
...
PMID:Sequence homology around the biotin-binding site of human propionyl-CoA carboxylase and pyruvate carboxylase. 355 48

Among more than 7000 mutants of Saccharomyces cerevisiae, requiring saturated fatty acids, 61 acetyl-CoA-carboxylase-deficient strains have been identified. According to their mutual complementation characteristics these mutants have been assigned to two different genes, acc1 and acc2. Both acetyl-CoA carboxylase genes are unlinked to each other and to the fatty acids synthetase genes fas1 and fas2. The acetyl-CoA carboxylases of several acc1 and acc2 mutants have been purified and assayed for their overall and component enzyme activities. Besides overall acetyl-CoA carboxylation, which was lost in all cases, both component enzymes, biotin carboxylase and transcarboxylase, were simultaneously affected in most mutants, though often to a different relative extent. Similarly, the comparison of biochemical and genetic complementation data revealed no basis for a clear distinction between specific biotin carboxylase and transcarboxylase mutants. These results suggest that acc1 is a cluster gene coding for a multifunctional protein harboring both acetyl-CoA carboxylase component enzyme activities on the same polypeptide chain. The acetyl-CoA carboxylase isolated from acc2 mutants was free of biotin. Correspondingly, biotin:apoacetyl-CoA-carboxylase ligase activity was missing in acc2 mutants. Therefore, it is concluced that the primary defect in acc2 mutants is in the biotin:apocarboxylase ligase. In agreement with this conclusion, the acc2 acetyl-CoA carboxylase can be activated, in the presence of biotin and ATP, by ligase preparations from wild-type or acc1 mutant cells. By the use of these mutants, evidence was obtained that in vivo the biotinylation of both acetyl-CoA carboxylase and pyruvate carboxylase is catalyzed by the same ligase.
...
PMID:Yeast mutants defective in acetyl-coenzyme A carboxylase and biotin: apocarboxylase ligase. 610 18

The complete amino acid sequence of 3T3-L1 adipocyte pyruvate carboxylase (PC) [pyruvate:carbon-dioxide ligase (ADP-forming), EC 6.4.1.1] has been deduced from sequencing overlapping cDNA clones obtained from an adipocyte cDNA library constructed in the lambda Zap vector. The encoding mRNA for PC promoter contains 4067 nt, including a 3534-nt coding sequence and noncoding regions of 100 and 433 nt at the 5' and 3' ends, respectively. The biotinylated lysine of the encoded PC promoter (1178 amino acids with a calculated M(r) of apocarboxylase = 129,784) is located 35 residues from the COOH-terminal end and, as in most other biotin enzymes, is in the consensus sequence AMKM. The adipocyte PC is closely similar (53% identity) to the yeast enzyme and contains different segments that are homologous with regions from the biotin carboxylase component of Escherichia coli acetyl-CoA carboxylase, the keto acid-binding subunits of Propionibacterium shermanii oxaloacetate transcarboxylase and Klebsiella pneumoniae oxaloacetate decarboxylase, and to the biotin carboxyl-carrier protein of the bacterial biotin enzymes. In addition to the putative mitochondrial targeting signal, functional domains are readily identifiable in the sequence and are in the following order: biotin carboxylase-carboxyltransferase-biotin carboxyl-carrier protein, as proposed for yeast PC.
...
PMID:Adipose pyruvate carboxylase: amino acid sequence and domain structure deduced from cDNA sequencing. 844 88

Sequencing of the gene encoding a pyruvate carboxylase-like protein from the amitochondrial eukaryote Giardia intestinalis revealed a 1,338 aa protein composed of acetyl-CoA carboxyltransferase (ACCT), pyruvate carboxyltransferase (PycB), and biotin carboxyl carrier protein (BCCP) domains, linked in a single polypeptide chain. This particular domain combination has been previously seen only in the methylmalonyl-CoA:pyruvate transcarboxylase from Propionibacterium freudenreichii, where each of these domains is encoded by an individual gene and forms a separate subunit. To get an insight into the evolutionary origin and biochemical function of the G. intestinalis enzyme, we compared its domain composition to those of other biotin-dependent enzymes and performed a phylogenetic analysis of each of its domains. The results obtained indicate that: (1) evolution of the BCCP domain included several domain fusion events, leading to the ACCT-BCCP and PycB-BCCP domain combinations; (2) fusions of the PycB and BCCP domains in pyruvate carboxylases and oxaloacetate decarboxylases occurred on several independent occasions in different prokaryotic lineages, probably due to selective pressure towards co-expression of these genes, and (3) because newly sequenced biotin-dependent enzymes are often misannotated in sequence databases, their annotation as either carboxylases, decarboxylases, or transcarboxylases has to rely on detailed analysis of their domain composition, operon organization of the corresponding genes, gene content in the particular genome, and phylogenetic analysis.
...
PMID:Phylogenomic analysis of the Giardia intestinalis transcarboxylase reveals multiple instances of domain fusion and fission in the evolution of biotin-dependent enzymes. 1276 47

The biotin carboxylase family is comprised of a group of enzymes that utilize a covalently bound prosthetic group, biotin, as a cofactor. These enzymes, which include acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, geranoyl-CoA carboxylase, oxaloacetate decarboxylase, methylmalonyl-CoA decarboxylase, transcarboxylase and urea amidolyase, are found in diverse biosynthetic pathways in both pro-karyotes and eukaryotes. The reactions catalyzed by most members of this group of enzymes share two common features: (1) carboxylation of biotin, apparently via the formation of a carboxyphosphate intermediate, followed by (2) transcarboxylation of CO(2) from biotin to specific acceptor molecules to yield different products. Structural determinations by NMR and X-ray crystallography, complemented by mutagenesis studies, have identified some motifs that are structurally or catalytically important. Analysis of the amino acid sequences of a number of biotin carboxylases not only shows remarkable similarities within certain domains but also that there appears to have been domain rearrangements between groups of carboxylases. Acyl-coenzyme A derivatives, which bind either as substrates or as allosteric regulators of the biotin carboxylases, do not appear to share any of the CoA binding motifs that have been identified in other CoA-SH/acyl-CoA binding proteins. Further comparisons of biotin-dependent carboxylases with other groups of enzymes in the protein data bank reveal that this family of biotin enzymes has strong similarities in specific domains to a number of ATP-utilizing enzymes and to the lipoyl-containing enzymes. These structural homologies are so extensive as to be highly suggestive of evolutionary relationships between biotin carboxylases and these other enzymes.
...
PMID:The biotin enzyme family: conserved structural motifs and domain rearrangements. 1276 20

The enzyme transcarboxylase (TC) catalyzes an unusual reaction; TC transfers a carboxylate group from methylmalonyl-CoA to pyruvate to form oxaloacetate and propionyl-CoA. Remarkably, to perform this task in Propionii bacteria Nature has created a large assembly made up of 30 polypeptides that totals 1.2 million daltons. In this nanomachine the catalytic machinery is repeated 6-12 times over using ordered arrays of replicated subunits. The latter are sites of the half reactions. On the so-called 12S subunit a biotin cofactor accepts carboxylate, - CO2- , from methylmalonyl-CoA. The carboxylated-biotin then translocates to a second subunit, the 5S, to deliver the carboxylate to pyruvate. We have not yet characterized the intact nanomachine, however, using a battery of biophysical techniques, we have been able to derive novel,and sometimes unexpected, structural and mechanistic insights into the 12S and 5S subunits. Similar insights have been obtained for the small 1.3S subunit that acts as the biotin carrier linking the 12S and 5S forms. Interestingly, some of these insights gained for the 12S and 5S subunits carry over to related mammalian enzymes such as human propionyl-CoA carboxylase and human pyruvate carboxylase, respectively, to provide a rationale for their malfunction in disease-related mutations.
...
PMID:Transcarboxylase: one of nature's early nanomachines. 1581 55


1 2 Next >>

---