Summary: Catalytically active enzymes that are formed by the combination of an apoenzyme (APOENZYMES) and its appropriate cofactors and prosthetic groups.

Top Publications

  1. Stone M, Mihalusova M, O Connor C, Prathapam R, Collins K, Zhuang X. Stepwise protein-mediated RNA folding directs assembly of telomerase ribonucleoprotein. Nature. 2007;446:458-61 pubmed
    ..These results identify the RNA folding pathway during telomerase biogenesis and define the mechanism of action for an essential telomerase holoenzyme protein. ..
  2. Huang C, Sadre Bazzaz K, Shen Y, Deng B, Zhou Z, Tong L. Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase. Nature. 2010;466:1001-5 pubmed publisher
    ..basis for understanding the large collection of disease-causing mutations in PCC and is relevant for the holoenzymes of other biotin-dependent carboxylases, including 3-methylcrotonyl-CoA carboxylase (MCC) and eukaryotic acetyl-..
  3. Burrows P, Wigneshweraraj S, Buck M. Protein-DNA interactions that govern AAA+ activator-dependent bacterial transcription initiation. J Mol Biol. 2008;375:43-58 pubmed
    ..These results significantly advance our current understanding of the structural transitions occurring at bacterial promoters, where regulation occurs at the DNA melting step. ..
  4. Xu Y, Xing Y, Chen Y, Chao Y, Lin Z, Fan E, et al. Structure of the protein phosphatase 2A holoenzyme. Cell. 2006;127:1239-51 pubmed
    ..This structure reveals significant ramifications for understanding the function and regulation of PP2A. ..
  5. Tsai H, Masquida B, Biswas R, Westhof E, Gopalan V. Molecular modeling of the three-dimensional structure of the bacterial RNase P holoenzyme. J Mol Biol. 2003;325:661-75 pubmed
    ..These models are consistent with results from previous studies and provide both structural and mechanistic insights into the functioning of this unique catalytic RNP complex. ..
  6. Kurimchak A, Grana X. PP2A holoenzymes negatively and positively regulate cell cycle progression by dephosphorylating pocket proteins and multiple CDK substrates. Gene. 2012;499:1-7 pubmed publisher
    ..Other functions of PP2A during the cell cycle will be discussed in brief, as comprehensive reviews on this topic have been published recently (De Wulf et al., 2009; Wurzenberger and Gerlich, 2011). ..
  7. Witkin K, Collins K. Holoenzyme proteins required for the physiological assembly and activity of telomerase. Genes Dev. 2004;18:1107-18 pubmed
    ..These findings demonstrate that telomerase holoenzyme proteins other than TERT play critical roles in RNP biogenesis and function. ..
  8. Cho U, Xu W. Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme. Nature. 2007;445:53-7 pubmed
    ..Together, our structural results establish a crucial foundation for understanding PP2A assembly, substrate recruitment and regulation. ..
  9. Gupta Y, Yang L, Chan S, Samuelson J, Xu S, Aggarwal A. Structural insights into the assembly and shape of Type III restriction-modification (R-M) EcoP15I complex by small-angle X-ray scattering. J Mol Biol. 2012;420:261-8 pubmed publisher
    ..We discuss the implications of our model for EcoP15I action, whereby the Res subunits may come together and form a "sliding clamp" around the DNA. ..

More Information


  1. Wegscheid B, Hartmann R. In vivo and in vitro investigation of bacterial type B RNase P interaction with tRNA 3'-CCA. Nucleic Acids Res. 2007;35:2060-73 pubmed
    ..We conclude that the observed in vivo defects upon disruption of the CCA interaction are either due to a global deceleration in ptRNA maturation or severe inhibition of 5'-maturation for a ptRNA subset. ..
  2. Xu Y, Chen Y, Zhang P, Jeffrey P, Shi Y. Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated Tau dephosphorylation. Mol Cell. 2008;31:873-85 pubmed publisher
    ..The beta propeller latches onto the ridge of the PP2A scaffold subunit with the help of a protruding beta hairpin arm. Structure-guided mutagenesis studies revealed the underpinnings of PP2A-mediated dephosphorylation of Tau. ..
  3. Rosenberg O, Deindl S, Sung R, Nairn A, Kuriyan J. Structure of the autoinhibited kinase domain of CaMKII and SAXS analysis of the holoenzyme. Cell. 2005;123:849-60 pubmed
  4. Day Storms J, Niranjanakumari S, Fierke C. Ionic interactions between PRNA and P protein in Bacillus subtilis RNase P characterized using a magnetocapture-based assay. RNA. 2004;10:1595-608 pubmed
    ..Finally, pre-tRNAasp (but not tRNAasp) stabilizes the PRNA*P protein complex, as predicted by the direct interaction between the P protein and pre-tRNA leader. ..
  5. Bose D, Pape T, Burrows P, Rappas M, Wigneshweraraj S, Buck M, et al. Organization of an activator-bound RNA polymerase holoenzyme. Mol Cell. 2008;32:337-46 pubmed publisher
  6. Abdulovic A, Hile S, Kunkel T, Eckert K. The in vitro fidelity of yeast DNA polymerase ? and polymerase ? holoenzymes during dinucleotide microsatellite DNA synthesis. DNA Repair (Amst). 2011;10:497-505 pubmed publisher
    ..address this gap in knowledge by measuring the fidelity of recombinant yeast polymerase ? (Pol ?) and ? (Pol ?) holoenzymes during synthesis of a [GT/CA] microsatellite...
  7. Jayadeva G, Kurimchak A, Garriga J, Sotillo E, Davis A, Haines D, et al. B55alpha PP2A holoenzymes modulate the phosphorylation status of the retinoblastoma-related protein p107 and its activation. J Biol Chem. 2010;285:29863-73 pubmed publisher
    ..Our data also suggest targeted selectivity in the interaction of pocket proteins with distinct PP2A holoenzymes, which is likely necessary for simultaneous pocket protein activation.
  8. Zhou Z, Hashimoto Y, Shiraki K, Kobayashi M. Discovery of posttranslational maturation by self-subunit swapping. Proc Natl Acad Sci U S A. 2008;105:14849-54 pubmed publisher
    ..This is a posttranslational maturation process different from general mechanisms of metallocenter biosynthesis known so far: the unexpected behavior of a protein in a protein complex, which we named "self-subunit swapping." ..
  9. Kvissel A, Ørstavik S, Øistad P, Rootwelt T, Jahnsen T, Skålhegg B. Induction of Cbeta splice variants and formation of novel forms of protein kinase A type II holoenzymes during retinoic acid-induced differentiation of human NT2 cells. Cell Signal. 2004;16:577-87 pubmed
    ..induction of a number of neuronal-specific Cbeta splice variants that together with RIIbeta form novel PKAII holoenzymes. Formation of novel PKAII holoenzymes may imply specific PKA features which may have consequences for the ..
  10. Perederina A, Esakova O, Quan C, Khanova E, Krasilnikov A. Eukaryotic ribonucleases P/MRP: the crystal structure of the P3 domain. EMBO J. 2010;29:761-9 pubmed publisher
    ..in RNases P/MRP and possible functions of the P3 domains and proteins bound to them in the stabilization of the holoenzymes' structures as well as in interactions with substrates...
  11. Kim C, Cheng C, Saldanha S, Taylor S. PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation. Cell. 2007;130:1032-43 pubmed
    ..Mutagenesis of these residues demonstrates their importance for PKA activation. Our structural insights, combined with the mutagenesis results, provide a molecular mechanism for the ordered and cooperative activation of PKA by cAMP. ..
  12. Young B, Gruber T, Gross C. Minimal machinery of RNA polymerase holoenzyme sufficient for promoter melting. Science. 2004;303:1382-4 pubmed
    ..Our results support the model that capture of nontemplate bases extruded from the DNA helix underlies the melting process. ..
  13. Zhang P, Smith Nguyen E, Keshwani M, Deal M, Kornev A, Taylor S. Structure and allostery of the PKA RII? tetrameric holoenzyme. Science. 2012;335:712-6 pubmed publisher
    ..The quaternary structure of the RII? tetramer differs appreciably from our model of the RI? tetramer, confirming the small-angle x-ray scattering prediction that the structures of each PKA tetramer are different. ..
  14. Sexton A, Youmans D, Collins K. Specificity requirements for human telomere protein interaction with telomerase holoenzyme. J Biol Chem. 2012;287:34455-64 pubmed publisher
  15. Wiesler S, Burrows P, Buck M. A dual switch controls bacterial enhancer-dependent transcription. Nucleic Acids Res. 2012;40:10878-92 pubmed publisher
  16. Xing Y, Xu Y, Chen Y, Jeffrey P, Chao Y, Lin Z, et al. Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins. Cell. 2006;127:341-53 pubmed
    ..These structures, together with biochemical analyses, reveal significant insights into PP2A function and serve as a framework for deciphering the diverse roles of PP2A in cellular physiology. ..
  17. Cunningham D, Collins K. Biological and biochemical functions of RNA in the tetrahymena telomerase holoenzyme. Mol Cell Biol. 2005;25:4442-54 pubmed
    ..We also characterized the in vitro activity of the telomerase holoenzymes reconstituted with TER variants, following RNA-based RNP affinity purification from cell extracts...
  18. Thaler C, Koushik S, Puhl H, Blank P, Vogel S. Structural rearrangement of CaMKIIalpha catalytic domains encodes activation. Proc Natl Acad Sci U S A. 2009;106:6369-74 pubmed publisher
    ..Our data support the existence of catalytic domain pairs, and glutamate receptor activation in neurons triggered an increase in anisotropy consistent with a structural transition from a paired to unpaired conformation. ..
  19. Min B, Collins K. Multiple mechanisms for elongation processivity within the reconstituted tetrahymena telomerase holoenzyme. J Biol Chem. 2010;285:16434-43 pubmed publisher
    ..Overall, our findings reveal multiple mechanisms and multiple surfaces of protein-DNA and protein-protein interaction that give rise to elongation processivity in the synthesis of a single-stranded nucleic acid product...
  20. Dennis M, Browning K. Differential phosphorylation of plant translation initiation factors by Arabidopsis thaliana CK2 holoenzymes. J Biol Chem. 2009;284:20602-14 pubmed publisher
    ..Recombinant A. thaliana CK2beta subunits spontaneously dimerize and assemble into holoenzymes in the presence of either CK2alpha1 or CK2alpha2 and exhibit autophosphorylation...
  21. Murakami K, Darst S. Bacterial RNA polymerases: the wholo story. Curr Opin Struct Biol. 2003;13:31-9 pubmed
    ..Comparisons with structural analyses of evolutionarily unrelated RNA polymerases reveal unexpected general features of the initiation process. ..
  22. Gaal T, Mandel M, Silhavy T, Gourse R. Crl facilitates RNA polymerase holoenzyme formation. J Bacteriol. 2006;188:7966-70 pubmed
    ..Our results suggest that Crl facilitates holoenzyme formation, the first positive regulator identified with this mechanism of action. ..
  23. Lander G, Estrin E, Matyskiela M, Bashore C, Nogales E, Martin A. Complete subunit architecture of the proteasome regulatory particle. Nature. 2012;482:186-91 pubmed publisher
    ..We provide a structural basis for the ability of the proteasome to degrade a diverse set of substrates and thus regulate vital cellular processes. ..
  24. McGovern S, Shoichet B. Information decay in molecular docking screens against holo, apo, and modeled conformations of enzymes. J Med Chem. 2003;46:2895-907 pubmed
  25. Rosenfeld K, Ziv T, Goldin S, Glaser F, Manor H. Mapping of DNA binding sites in the Tetrahymena telomerase holoenzyme proteins by UV cross-linking and mass spectrometry. J Mol Biol. 2011;410:77-92 pubmed publisher
    ..Our study constitutes the first direct mapping of DNA interaction sites in telomerase holoenzyme complexes. This mapping represents a significant contribution to the understanding of the mechanism of telomere extension by telomerase. ..
  26. Richards R, Wu H, Trantirek L, O Connor C, Collins K, Feigon J. Structural study of elements of Tetrahymena telomerase RNA stem-loop IV domain important for function. RNA. 2006;12:1475-85 pubmed
    ..The results suggest that during holoenzyme assembly the protein p65 recognizes a bend in stem IV, and this binding to central stem IV helps to position the structured loop IV for interaction with TERT and other region(s) of TER. ..
  27. Singh M, Wang Z, Koo B, Patel A, Cascio D, Collins K, et al. Structural basis for telomerase RNA recognition and RNP assembly by the holoenzyme La family protein p65. Mol Cell. 2012;47:16-26 pubmed publisher
    ..Additionally, our studies define a structurally homologous domain (xRRM) in genuine La and LARP7 proteins and suggest a general mode of RNA binding for biogenesis of their diverse RNA targets...
  28. O Connor C, Collins K. A novel RNA binding domain in tetrahymena telomerase p65 initiates hierarchical assembly of telomerase holoenzyme. Mol Cell Biol. 2006;26:2029-36 pubmed
    ..These findings elucidate an extensive network of p65-TER recognition specificity and define a novel p65 RNA binding domain that initiates telomerase holoenyzme biogenesis. ..
  29. Belogurov G, Vassylyeva M, Sevostyanova A, Appleman J, Xiang A, Lira R, et al. Transcription inactivation through local refolding of the RNA polymerase structure. Nature. 2009;457:332-5 pubmed publisher
    ..The universally conserved switch-2 may have the same role in all multisubunit RNAPs. ..
  30. Wegscheid B, Condon C, Hartmann R. Type A and B RNase P RNAs are interchangeable in vivo despite substantial biophysical differences. EMBO Rep. 2006;7:411-7 pubmed
  31. Buck A, Dalby A, Poole A, Kazantsev A, Pace N. Protein activation of a ribozyme: the role of bacterial RNase P protein. EMBO J. 2005;24:3360-8 pubmed
    ..each protein in complex with its cognate and noncognate RNA, we show that differences between the two types of holoenzymes reside primarily in the RNA and not the protein components of each...
  32. Chlenov M, Masuda S, Murakami K, Nikiforov V, Darst S, Mustaev A. Structure and function of lineage-specific sequence insertions in the bacterial RNA polymerase beta' subunit. J Mol Biol. 2005;353:138-54 pubmed
  33. Orstavik S, Funderud A, Hafte T, Eikvar S, Jahnsen T, Skålhegg B. Identification and characterization of novel PKA holoenzymes in human T lymphocytes. FEBS J. 2005;272:1559-67 pubmed
    ..demonstrated that both C alpha1 and C beta2 associate with RI alpha and RII alpha to form PKAI and PKAII holoenzymes. Moreover, Anti-C beta2 immunoprecipitation revealed that C alpha1 coimmunoprecipitates with C beta2...
  34. Corbett K, Benedetti P, Berger J. Holoenzyme assembly and ATP-mediated conformational dynamics of topoisomerase VI. Nat Struct Mol Biol. 2007;14:611-9 pubmed publisher
    ..These data afford important insights into the mechanisms of topo VI and related proteins, including type IIA topoisomerases and the Spo11 meiotic recombination endonuclease...
  35. Feklistov A, Barinova N, Sevostyanova A, Heyduk E, Bass I, Vvedenskaya I, et al. A basal promoter element recognized by free RNA polymerase sigma subunit determines promoter recognition by RNA polymerase holoenzyme. Mol Cell. 2006;23:97-107 pubmed
    ..2 and directs transcription initiation even in the absence of the -35 promoter element. Thus, recognition of bacterial promoters is controlled by independent interactions of sigma with multiple basal promoter elements...
  36. Li D, Willkomm D, Schön A, Hartmann R. RNase P of the Cyanophora paradoxa cyanelle: a plastid ribozyme. Biochimie. 2007;89:1528-38 pubmed
    ..Likely related to this low robustness, extensive structural changes towards an E. coli-type P5-7/P15-17 subdomain as a canonical interaction site for tRNA 3'-CCA termini could not be coaxed into increased ribozyme activity. ..
  37. Mekler V, Pavlova O, Severinov K. Interaction of Escherichia coli RNA polymerase ?70 subunit with promoter elements in the context of free ?70, RNA polymerase holoenzyme, and the ?'-?70 complex. J Biol Chem. 2011;286:270-9 pubmed publisher
    ..The new fluorescent assay, which we call a protein beacon assay, will be instrumental in quantitative dissection of fine details of RNAP interactions with promoters. ..
  38. Gallardo F, Chartrand P. Telomerase biogenesis: The long road before getting to the end. RNA Biol. 2008;5:212-5 pubmed
    ..These studies revealed that telomerase biogenesis is a highly dynamic process, which is regulated in space and time, and which ultimately affects how cells maintain genome integrity. ..
  39. Tsai H, Pulukkunat D, Woznick W, Gopalan V. Functional reconstitution and characterization of Pyrococcus furiosus RNase P. Proc Natl Acad Sci U S A. 2006;103:16147-52 pubmed
    ..archaeal/eukaryal RNase P catalysis, in contrast to their bacterial relative, in vitro reconstitution of these holoenzymes is a prerequisite...
  40. Sents W, Ivanova E, Lambrecht C, Haesen D, Janssens V. The biogenesis of active protein phosphatase 2A holoenzymes: a tightly regulated process creating phosphatase specificity. FEBS J. 2013;280:644-61 pubmed publisher
    ..The composition of heterotrimeric PP2A holoenzymes, resulting from the combinatorial assembly of a catalytic C subunit, a structural A subunit, and regulatory B-..
  41. Roelofs J, Park S, Haas W, Tian G, McAllister F, Huo Y, et al. Chaperone-mediated pathway of proteasome regulatory particle assembly. Nature. 2009;459:861-5 pubmed publisher
    ..In addition, competition between the RP chaperones and the CP for Rpt engagement may explain the release of RP chaperones as proteasomes mature. ..
  42. Boettcher A, Wu J, Kim C, Yang J, Bruystens J, Cheung N, et al. Realizing the allosteric potential of the tetrameric protein kinase A RI? holoenzyme. Structure. 2011;19:265-76 pubmed publisher
    PKA holoenzymes containing two catalytic (C) subunits and a regulatory (R) subunit dimer are activated cooperatively by cAMP...
  43. Fenton M, Gralla J. Effect of DNA bases and backbone on sigma70 holoenzyme binding and isomerization using fork junction probes. Nucleic Acids Res. 2003;31:2745-50 pubmed
    ..In contrast various upstream elements cooperate primarily to stimulate binding. Features and positions most important for these effects are identified. ..
  44. Eckert B, Collins K. Roles of telomerase reverse transcriptase N-terminal domain in assembly and activity of Tetrahymena telomerase holoenzyme. J Biol Chem. 2012;287:12805-14 pubmed publisher
    ..Our results add to the understanding of telomerase holoenzyme architecture and TERT domain functions with direct implications for the unique mechanism of single-stranded repeat synthesis. ..
  45. Widau R, Jin Y, Dixon S, Wadzinski B, Gallagher P. Protein phosphatase 2A (PP2A) holoenzymes regulate death-associated protein kinase (DAPK) in ceramide-induced anoikis. J Biol Chem. 2010;285:13827-38 pubmed publisher
    ..These phosphatase holoenzymes dephosphorylate DAPK at Ser-308 in vitro and in vivo resulting in enhanced kinase activity of DAPK...
  46. Chao L, Stratton M, Lee I, Rosenberg O, Levitz J, Mandell D, et al. A mechanism for tunable autoinhibition in the structure of a human Ca2+/calmodulin- dependent kinase II holoenzyme. Cell. 2011;146:732-45 pubmed publisher
    ..This equilibrium between autoinhibited states provides a simple mechanism for tuning the calcium response without changes in either the hub or the kinase domains. ..
  47. Augustine A, Quintanar L, Stoj C, Kosman D, Solomon E. Spectroscopic and kinetic studies of perturbed trinuclear copper clusters: the role of protons in reductive cleavage of the O-O bond in the multicopper oxidase Fet3p. J Am Chem Soc. 2007;129:13118-26 pubmed
    ..A mechanism is developed where these second sphere residues participate in the proton assisted reductive cleavage of the O-O bond at the TNC. ..
  48. Min B, Collins K. An RPA-related sequence-specific DNA-binding subunit of telomerase holoenzyme is required for elongation processivity and telomere maintenance. Mol Cell. 2009;36:609-19 pubmed publisher
    ..The RPA-like p82 subunit binds sequence specifically to multiple telomeric repeats. These discoveries establish the existence of a telomerase holoenzyme processivity subunit with sequence-specific DNA binding. ..
  49. Perederina A, Khanova E, Quan C, Berezin I, Esakova O, Krasilnikov A. Interactions of a Pop5/Rpp1 heterodimer with the catalytic domain of RNase MRP. RNA. 2011;17:1922-31 pubmed publisher
    ..The Pop5/Rpp1 binding site corresponds to the protein binding site in bacterial RNase P RNA. Structural and evolutionary roles of the Pop5/Rpp1 heterodimer in RNases P and MRP are discussed. ..
  50. Chilkova O, Stenlund P, Isoz I, Stith C, Grabowski P, Lundström E, et al. The eukaryotic leading and lagging strand DNA polymerases are loaded onto primer-ends via separate mechanisms but have comparable processivity in the presence of PCNA. Nucleic Acids Res. 2007;35:6588-97 pubmed
    ..We conclude that Pol epsilon and Pol delta exhibit comparable processivity, but are loaded on the primer-end via different mechanisms. ..
  51. Reiter N, Osterman A, Torres Larios A, Swinger K, Pan T, MONDRAGON A. Structure of a bacterial ribonuclease P holoenzyme in complex with tRNA. Nature. 2010;468:784-9 pubmed publisher
    ..The active site structure and conserved RNase P-tRNA contacts suggest a universal mechanism of catalysis by RNase P. ..
  52. Diskar M, Zenn H, Kaupisch A, Prinz A, Herberg F. Molecular basis for isoform-specific autoregulation of protein kinase A. Cell Signal. 2007;19:2024-34 pubmed
    ..Only PKA type II or mutant PKA type I holoenzymes (P(0): Ser or Asp) are able to dissociate fully upon maximally elevated intracellular cAMP...
  53. Murakami K, Masuda S, Campbell E, Muzzin O, Darst S. Structural basis of transcription initiation: an RNA polymerase holoenzyme-DNA complex. Science. 2002;296:1285-90 pubmed publisher
    ..The structure explains how holoenzyme recognizes promoters containing variably spaced -10 and -35 elements and provides the basis for models of the closed and open promoter complexes...