Experts and Doctors on multienzyme complexes in Detroit, Michigan, United States


Locale: Detroit, Michigan, United States
Topic: multienzyme complexes

Top Publications

  1. Hong Y, Varanasi U, Yang W, Leff T. AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability. J Biol Chem. 2003;278:27495-501 pubmed
    ..These results demonstrate that HNF4alpha is a downstream target of AMPK and raise the possibility that one of the effects of AMPK activation is reduced expression of HNF4alpha target genes. ..
  2. Rosen B, Weigel U, Monticello R, Edwards B. Molecular analysis of an anion pump: purification of the ArsC protein. Arch Biochem Biophys. 1991;284:381-5 pubmed
    ..The arsC gene was cloned behind a strong promoter and expressed at high levels. The ArsC protein was purified and crystallized. ..
  3. Rosen B. The plasmid-encoded arsenical resistance pump: an anion-translocating ATPase. Res Microbiol. 1990;141:336-41 pubmed
    ..This two-subunit enzyme produces resistance to arsenite and antimonite. A third gene, arsC, expands the substrate specificity to allow for arsenate pumping and resistance. ..
  4. Kim H, Kelly R, Evans D. The structural organization of the hamster multifunctional protein CAD. Controlled proteolysis, domains, and linkers. J Biol Chem. 1992;267:7177-84 pubmed
    ..These studies provide a more detailed map of the structural organization of the CAD polypeptide. ..
  5. San Francisco M, Tisa L, Rosen B. Identification of the membrane component of the anion pump encoded by the arsenical resistance operon of R-factor R773. Mol Microbiol. 1989;3:15-21 pubmed
    ..In addition to the previously identified ArsA and ArsC proteins, the cells synthesized an inner membrane protein with an apparent mass of 36 kD identified as the ArsB protein. ..
  6. Carlin A, Shi W, Dey S, Rosen B. The ars operon of Escherichia coli confers arsenical and antimonial resistance. J Bacteriol. 1995;177:981-6 pubmed
    ..Expression of the ars genes was inducible by arsenite. By Southern hybridization, the operon was found in all strains of E. coli examined but not in Salmonella typhimurium, Pseudomonas aeruginosa, or Bacillus subtilis. ..
  7. Mukhopadhyay R, Rosen B. Arsenate reductases in prokaryotes and eukaryotes. Environ Health Perspect. 2002;110 Suppl 5:745-8 pubmed
    ..The yeast Acr2p has an active site motif HC(X)(5)R that is conserved in protein phosphotyrosine phosphatases and rhodanases, suggesting that these three groups of enzymes may have evolved from an ancestral oxyanion-binding protein. ..
  8. Shi J, Mukhopadhyay R, Rosen B. Identification of a triad of arginine residues in the active site of the ArsC arsenate reductase of plasmid R773. FEMS Microbiol Lett. 2003;227:295-301 pubmed
    ..The data support the hypothesis that this triad of arginine residues is involved in arsenate binding and transition-state stabilization. ..
  9. Bein K, Simmer J, Evans D. Molecular cloning of a cDNA encoding the amino end of the mammalian multifunctional protein CAD and analysis of the 5'-flanking region of the CAD gene. J Biol Chem. 1991;266:3791-9 pubmed
    ..The CAD mRNA is 7.5 kb in length and has 6675 bp of coding sequence and about 200 bp and 600 bp of untranslated sequence at the 5' and 3' ends, respectively. ..

More Information


  1. Mukhopadhyay R, Ho Y, Swiatek P, Rosen B, Bhattacharjee H. Targeted disruption of the mouse Asna1 gene results in embryonic lethality. FEBS Lett. 2006;580:3889-94 pubmed
    ..However, early embryonic lethality was observed in homozygous Asna1 knockout embryos, between E3.5 (E=embryonic day) and E8.5 stage. These findings indicate that Asna1 plays a crucial role during early embryonic development. ..
  2. Evans D, Guy H. Mammalian pyrimidine biosynthesis: fresh insights into an ancient pathway. J Biol Chem. 2004;279:33035-8 pubmed
  3. Martin P, DeMel S, Shi J, Gladysheva T, Gatti D, Rosen B, et al. Insights into the structure, solvation, and mechanism of ArsC arsenate reductase, a novel arsenic detoxification enzyme. Structure. 2001;9:1071-81 pubmed
  4. Zhou T, Radaev S, Rosen B, Gatti D. Structure of the ArsA ATPase: the catalytic subunit of a heavy metal resistance pump. EMBO J. 2000;19:4838-45 pubmed publisher
    ..The relative positions of the NBS and the inferred mechanism of allosteric activation of ArsA provide a useful model for the interaction of the catalytic domains in other transport ATPases...
  5. Bhattacharjee H, Ho Y, Rosen B. Genomic organization and chromosomal localization of the Asna1 gene, a mouse homologue of a bacterial arsenic-translocating ATPase gene. Gene. 2001;272:291-9 pubmed
    ..All splice sites conform to the GT-AG rule, except for the splice donor site of intron 4 that is GC instead of GT. Fluorescence in situ hybridization indicates that the Asna1 gene is localized in the C3-D1 region of mouse chromosome 8. ..
  6. Wu J, Tisa L, Rosen B. Membrane topology of the ArsB protein, the membrane subunit of an anion-translocating ATPase. J Biol Chem. 1992;267:12570-6 pubmed
    ..The location of a periplasmic loop was determined from V8 protease digestion of an ArsA-ArsB chimera. From analysis of data from 26 fusions, a topological model of the ArsB protein with 12 membrane-spanning regions is proposed. ..
  7. Sigoillot F, Berkowski J, Sigoillot S, Kotsis D, Guy H. Cell cycle-dependent regulation of pyrimidine biosynthesis. J Biol Chem. 2003;278:3403-9 pubmed
    ..Thus, the cell cycle-dependent regulation of pyrimidine biosynthesis results from the sequential phosphorylation and dephosphorylation of CAD under the control of two important signaling cascades. ..
  8. Meng Y, Liu Z, Rosen B. As(III) and Sb(III) uptake by GlpF and efflux by ArsB in Escherichia coli. J Biol Chem. 2004;279:18334-41 pubmed
    ..We propose that the actual substrate of ArsB is a polymer of (AsO)(n), (SbO)(n), or a co-polymer of the two metalloids. ..
  9. Mukhopadhyay R, Shi J, Rosen B. Purification and characterization of ACR2p, the Saccharomyces cerevisiae arsenate reductase. J Biol Chem. 2000;275:21149-57 pubmed
    ..This suggests that during the catalytic cycle, Acr2p forms a mixed disulfide with GSH before being reduced by glutaredoxin to regenerate the active Acr2p reductase. ..
  10. Yang H, Cheng J, Finan T, Rosen B, Bhattacharjee H. Novel pathway for arsenic detoxification in the legume symbiont Sinorhizobium meliloti. J Bacteriol. 2005;187:6991-7 pubmed publisher
    ..Thus, AqpS confers arsenate resistance together with ArsC-catalyzed reduction. This is the first report of an aquaglyceroporin with a physiological function in arsenic resistance...
  11. Tisa L, Rosen B. Molecular characterization of an anion pump. The ArsB protein is the membrane anchor for the ArsA protein. J Biol Chem. 1990;265:190-4 pubmed
  12. Sigoillot F, Kotsis D, Serre V, Sigoillot S, Evans D, Guy H. Nuclear localization and mitogen-activated protein kinase phosphorylation of the multifunctional protein CAD. J Biol Chem. 2005;280:25611-20 pubmed
    ..Thus, the nuclear import of CAD appears to promote optimal cell growth. UMP synthase, the bifunctional protein that catalyzes the last two steps in the pathway, was also found in both the cytoplasm and nucleus. ..
  13. Tsutsumi S, Yanagawa T, Shimura T, Fukumori T, Hogan V, Kuwano H, et al. Regulation of cell proliferation by autocrine motility factor/phosphoglucose isomerase signaling. J Biol Chem. 2003;278:32165-72 pubmed
  14. Barrett K, Fang H, Gargano M, Markovich D, Kocarek T, Runge Morris M. Regulation of murine hepatic hydroxysteroid sulfotransferase expression in hyposulfatemic mice and in a cell model of 3'-phosphoadenosine-5'-phosphosulfate deficiency. Drug Metab Dispos. 2013;41:1505-13 pubmed publisher
    ..We propose that hyposulfatemia leads to hepatic PAPS depletion, which causes loss of SULT2A1 activity and results in accumulation of nonsulfated bile acids and FXR activation. ..
  15. Holland Staley C, Lee K, Clark D, Cunningham P. Aerobic activity of Escherichia coli alcohol dehydrogenase is determined by a single amino acid. J Bacteriol. 2000;182:6049-54 pubmed
    ..These findings suggest that adhE expression is also regulated posttranslationally and that strict regulation of alcohol dehydrogenase activity in E. coli is physiologically significant. ..
  16. Liu J, Rosen B. Ligand interactions of the ArsC arsenate reductase. J Biol Chem. 1997;272:21084-9 pubmed
    ..Cys-12 thiolate was also required. Thus the intrinsic fluorescence of Trp-11 provides a useful probe to investigate the mechanism of this novel reductase. ..
  17. Simmer J, Kelly R, Rinker A, Zimmermann B, Scully J, Kim H, et al. Mammalian dihydroorotase: nucleotide sequence, peptide sequences, and evolution of the dihydroorotase domain of the multifunctional protein CAD. Proc Natl Acad Sci U S A. 1990;87:174-8 pubmed
    ..Although these families may have arisen by convergent evolution, we favor a model involving DHOase gene duplication and insertion into an ancestral bifunctional locus...
  18. Mukhopadhyay R, Rosen B, Phung L, Silver S. Microbial arsenic: from geocycles to genes and enzymes. FEMS Microbiol Rev. 2002;26:311-25 pubmed
    ..Proposed reaction mechanisms in each case involve three cysteine thiols and S-As bond intermediates, so convergent evolution to similar mechanisms has taken place. ..
  19. Bhattacharjee H, Rosen B. Structure-function analysis of the ArsA ATPase: contribution of histidine residues. J Bioenerg Biomembr. 2001;33:459-68 pubmed
    ..The results indicate that no single histidine residue plays a direct role in catalysis, and the inhibition by DEPC may be caused by steric hindrance from the carbethoxy group. ..
  20. DeMel S, Shi J, Martin P, Rosen B, Edwards B. Arginine 60 in the ArsC arsenate reductase of E. coli plasmid R773 determines the chemical nature of the bound As(III) product. Protein Sci. 2004;13:2330-40 pubmed
    ..We propose that this intermediate is more stable than the monohydroxyarsenite intermediate of the native enzyme, resulting in slow release of product and, consequently, loss of activity. ..
  21. Oden K, Gladysheva T, Rosen B. Arsenate reduction mediated by the plasmid-encoded ArsC protein is coupled to glutathione. Mol Microbiol. 1994;12:301-6 pubmed
    ..Since ArsC-catalysed reduction of arsenate provides high level resistance, physical coupling of the ArsC reaction to efflux of the resulting arsenite is hypothesised. ..
  22. Simmer J, Kelly R, Scully J, Grayson D, Rinker A, Bergh S, et al. Mammalian aspartate transcarbamylase (ATCase): sequence of the ATCase domain and interdomain linker in the CAD multifunctional polypeptide and properties of the isolated domain. Proc Natl Acad Sci U S A. 1989;86:4382-6 pubmed
    ..The mammalian ATCase domain and the prokaryotic enzymes have virtually identical active-site residues and are likely to have the same tertiary fold. ..
  23. Lin Y, Yang J, Rosen B. ArsD: an As(III) metallochaperone for the ArsAB As(III)-translocating ATPase. J Bioenerg Biomembr. 2007;39:453-8 pubmed publisher
    ..It is proposed that ArsD residues Cys12, Cys13 and Cys18, but not Cys112, Cys113, Cys119 or Cys120, are required for delivery of As(III) to and activation of the ArsAB pump...
  24. Yang J, Rawat S, Stemmler T, Rosen B. Arsenic binding and transfer by the ArsD As(III) metallochaperone. Biochemistry. 2010;49:3658-66 pubmed publisher
    ..Neither MgADP nor MgATP-gamma-S could replace MgATP. These results suggest that transfer occurs with a conformation of ArsA that transiently forms during the catalytic cycle. ..
  25. Shen J, Hsu C, Kang B, Rosen B, Bhattacharjee H. The Saccharomyces cerevisiae Arr4p is involved in metal and heat tolerance. Biometals. 2003;16:369-78 pubmed
    ..It is proposed that under heat or metal stress, the soluble ATPase becomes membrane-associated, perhaps through interaction with a partner protein, and that this complex is involved in stress tolerance. ..
  26. Rosen B. Families of arsenic transporters. Trends Microbiol. 1999;7:207-12 pubmed
    ..Yeasts extrude arsenite using Acr3p, a plasma membrane carrier protein, or sequester it in vacuoles as the glutathione conjugate using Ycf1p, an ABC transporter...
  27. Ruan X, Bhattacharjee H, Rosen B. Cys-113 and Cys-422 form a high affinity metalloid binding site in the ArsA ATPase. J Biol Chem. 2006;281:9925-34 pubmed
  28. Ikonomov O, Sbrissa D, Fenner H, Shisheva A. PIKfyve-ArPIKfyve-Sac3 core complex: contact sites and their consequence for Sac3 phosphatase activity and endocytic membrane homeostasis. J Biol Chem. 2009;284:35794-806 pubmed publisher
    ..Based on these and other data, presented herein, we propose a model of domain interactions within the PAS core and their role in regulating the enzymatic activities. ..