Summary: The protein components of a number of complexes, such as enzymes (APOENZYMES), ferritin (APOFERRITINS), or lipoproteins (APOLIPOPROTEINS).

Top Publications

  1. Ayuso Tejedor S, Angarica V, Bueno M, Campos L, Abian O, Bernado P, et al. Design and structure of an equilibrium protein folding intermediate: a hint into dynamical regions of proteins. J Mol Biol. 2010;400:922-34 pubmed publisher
    ..The structure of the apoflavodoxin thermal intermediate suggests that the regions of natively folded proteins that are easily responsive to thermal activation may contain cores of intermediate hydrophobicity. ..
  2. Li T, Bonkovsky H, Guo J. Structural analysis of heme proteins: implications for design and prediction. BMC Struct Biol. 2011;11:13 pubmed publisher
  3. Samatova E, Melnik B, Balobanov V, Katina N, Dolgikh D, Semisotnov G, et al. Folding intermediate and folding nucleus for I-->N and U-->I-->N transitions in apomyoglobin: contributions by conserved and nonconserved residues. Biophys J. 2010;98:1694-702 pubmed publisher
  4. Nabuurs S, Westphal A, van Mierlo C. Noncooperative Formation of the off-pathway molten globule during folding of the alpha-beta parallel protein apoflavodoxin. J Am Chem Soc. 2009;131:2739-46 pubmed publisher
    ..The results presented here, together with those reported on the molten globule of alpha-lactalbumin, show that helical molten globules apparently fold in a noncooperative manner. ..
  5. Sreedhara A, Flengsrud R, Langsrud T, Kaul P, Prakash V, Vegarud G. Structural characteristic, pH and thermal stabilities of apo and holo forms of caprine and bovine lactoferrins. Biometals. 2010;23:1159-70 pubmed publisher
  6. Rosato Siri M, Badaracco M, Ortiz E, Belforte N, Clausi M, Soto E, et al. Oligodendrogenesis in iron-deficient rats: effect of apotransferrin. J Neurosci Res. 2010;88:1695-707 pubmed publisher
    ..Treatment with aTf almost completely reverted the effects of iron deficiency, both changing the migration pattern and increasing the number of mature cells in the CC and myelin formation. ..
  7. Nishimura C, Dyson H, Wright P. Consequences of stabilizing the natively disordered f helix for the folding pathway of apomyoglobin. J Mol Biol. 2011;411:248-63 pubmed publisher
    ..Rapid folding of the F helix stabilizes the central core of the misfolded intermediate and inhibits translocation of the H helix back to its native position, thereby decreasing the overall folding rate. ..
  8. Gumbart J, Wiener M, Tajkhorshid E. Coupling of calcium and substrate binding through loop alignment in the outer-membrane transporter BtuB. J Mol Biol. 2009;393:1129-42 pubmed publisher
    ..Based on our results, we suggest that the large size of cobalamin compared to other TonB-dependent transporter substrates explains the requirement of Ca(2+) binding for high-affinity substrate recruitment in BtuB. ..
  9. Banci L, Bertini I, Boca M, Calderone V, Cantini F, Girotto S, et al. Structural and dynamic aspects related to oligomerization of apo SOD1 and its mutants. Proc Natl Acad Sci U S A. 2009;106:6980-5 pubmed publisher
    ..The present results suggest that the investigation of the solution state coupled with that of the crystal state can provide major insights into SOD1 pathway toward oligomerization in relation to fALS. ..

More Information


  1. Feldkamp M, Yu L, Shea M. Structural and energetic determinants of apo calmodulin binding to the IQ motif of the Na(V)1.2 voltage-dependent sodium channel. Structure. 2011;19:733-47 pubmed publisher
    ..Thermodynamic and structural studies of CaM-Na(v)1.2(IQp) interactions show that apo and (Ca(2+))(4)-CaM adopt distinct conformations that both permit tight association with Na(v)1.2(IQp) during gating. ..
  2. Nabuurs S, Westphal A, aan den Toorn M, Lindhoud S, van Mierlo C. Topological switching between an alpha-beta parallel protein and a remarkably helical molten globule. J Am Chem Soc. 2009;131:8290-5 pubmed publisher
    ..Topological switching between unrelated protein structures is likely a general phenomenon in the protein structure universe. ..
  3. Wolfova J, Smatanova I, Brynda J, Mesters J, Lapkouski M, Kuty M, et al. Structural organization of WrbA in apo- and holoprotein crystals. Biochim Biophys Acta. 2009;1794:1288-98 pubmed publisher
    ..The results suggest that WrbAs are not a remote and unusual branch of the flavodoxin family as previously thought but rather a central member with unifying structural features. ..
  4. Ayuso Tejedor S, García Fandiño R, Orozco M, Sancho J, Bernado P. Structural analysis of an equilibrium folding intermediate in the apoflavodoxin native ensemble by small-angle X-ray scattering. J Mol Biol. 2011;406:604-19 pubmed publisher
    ..These simulations pointed to residues located in the cofactor and partner-protein recognition regions as the initial sites of denaturation and suggest a conformational adaptation as the mechanism of action in apoflavodoxin. ..
  5. Krishna A, Mandraju R, Kishore G, Kondapi A. An efficient targeted drug delivery through apotransferrin loaded nanoparticles. PLoS ONE. 2009;4:e7240 pubmed publisher
    ..The present study thus demonstrates that the direct-nano is highly efficacious in delivery of drug in a target specific manner with lower toxicity to heart, liver and kidney. ..
  6. Nabuurs S, de Kort B, Westphal A, van Mierlo C. Non-native hydrophobic interactions detected in unfolded apoflavodoxin by paramagnetic relaxation enhancement. Eur Biophys J. 2010;39:689-98 pubmed publisher
    ..Despite these difficulties, the spin-label data obtained here show that non-native contacts exist between transiently ordered structured elements in unfolded apoflavodoxin...
  7. Grenha R, Slamti L, Nicaise M, Refes Y, Lereclus D, Nessler S. Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR. Proc Natl Acad Sci U S A. 2013;110:1047-52 pubmed publisher
    ..Together with random mutagenesis experiments and interaction measurements using peptides from distinct pherogroups, this structural analysis allows us to propose a molecular mechanism for this functional switch...
  8. Moran D, Marone P, Bauter M, Soni M. Safety assessment of Apoaequorin, a protein preparation: subchronic toxicity study in rats. Food Chem Toxicol. 2013;57:1-10 pubmed publisher
    ..Based on the results of this study, the No Observed-Adverse-Effect Level (NOAEL) for Apoaequorin was determined as 666.7 mg/kg bw/day, the highest dose tested. ..
  9. Jiang R, Lopez V, Kelleher S, Lonnerdal B. Apo- and holo-lactoferrin are both internalized by lactoferrin receptor via clathrin-mediated endocytosis but differentially affect ERK-signaling and cell proliferation in Caco-2 cells. J Cell Physiol. 2011;226:3022-31 pubmed publisher
    ..The differential effects of apo- and holo-Lf are not due to differences in cellular internalization mechanisms. ..
  10. Laptenok S, Visser N, Engel R, Westphal A, van Hoek A, van Mierlo C, et al. A general approach for detecting folding intermediates from steady-state and time-resolved fluorescence of single-tryptophan-containing proteins. Biochemistry. 2011;50:3441-50 pubmed publisher
    ..9 kcal/mol and 6.8 kcal/mol, respectively) than WFF apoflavodoxin (4.1 kcal/mol) Hence, tryptophan residues contribute considerably to the 10.5 kcal/mol thermodynamic stability of native wild-type apoflavodoxin. ..
  11. Nabuurs S, Westphal A, van Mierlo C. Extensive formation of off-pathway species during folding of an alpha-beta parallel protein is due to docking of (non)native structure elements in unfolded molecules. J Am Chem Soc. 2008;130:16914-20 pubmed publisher
    ..Thus, rather than directing productive folding, conformational preorganization in the unfolded state of an alpha-beta parallel-type protein promotes off-pathway species formation. ..
  12. Landfried D, Vuletich D, Pond M, Lecomte J. Structural and thermodynamic consequences of b heme binding for monomeric apoglobins and other apoproteins. Gene. 2007;398:12-28 pubmed
    ..In several cases, the primary structure appeared biased toward a partially disordered binding pocket in the absence of the cofactor. ..
  13. Dessailly B, Lensink M, Orengo C, Wodak S. LigASite--a database of biologically relevant binding sites in proteins with known apo-structures. Nucleic Acids Res. 2008;36:D667-73 pubmed
    ..The datasets can be downloaded from the website as Schema-validated XML files or comma-separated flat files. ..
  14. Visser N, Westphal A, van Hoek A, van Mierlo C, Visser A, van Amerongen H. Tryptophan-tryptophan energy migration as a tool to follow apoflavodoxin folding. Biophys J. 2008;95:2462-9 pubmed publisher
    ..Apparently, apoFD's unfolded state is not a featureless statistical coil but contains well-defined substructures. The approach presented is a powerful tool to study protein folding. ..
  15. Engel R, Westphal A, Huberts D, Nabuurs S, Lindhoud S, Visser A, et al. Macromolecular crowding compacts unfolded apoflavodoxin and causes severe aggregation of the off-pathway intermediate during apoflavodoxin folding. J Biol Chem. 2008;283:27383-94 pubmed publisher
    ..Apparently, in the cell, apoflavodoxin requires the help of chaperones like Trigger Factor and the DnaK system for efficient folding. ..
  16. Badaracco M, Ortiz E, Soto E, Connor J, Pasquini J. Effect of transferrin on hypomyelination induced by iron deficiency. J Neurosci Res. 2008;86:2663-73 pubmed publisher
    ..Treatment of the ID animals with a single ICI of aTf stimulated myelination, producing a significant correction in the different biochemical parameters affected by ID. ..
  17. Jamin M. The folding process of apomyoglobin. Protein Pept Lett. 2005;12:229-34 pubmed
    ..The data are consistent with a linear U<->Ia<->Ib<->N model where compaction and structure are progressively acquired. ..
  18. Malmo C, Vilasi S, Iannuzzi C, Tacchi S, Cametti C, Irace G, et al. Tetracycline inhibits W7FW14F apomyoglobin fibril extension and keeps the amyloid protein in a pre-fibrillar, highly cytotoxic state. FASEB J. 2006;20:346-7 pubmed
    ..Thus, this inhibition keeps the W7FW14F mutant in a prefibrillar, highly cytotoxic state. In this respect, a careful usage of tetracycline as fibril inhibitor is indicated. ..
  19. Hariharan P, Liang W, Chou S, Chin D. A new model for ligand release. Role of side chain in gating the enediyne antibiotic. J Biol Chem. 2006;281:16025-33 pubmed
    ..Preliminary, biophysical characterization of mutant apoproteins by circular dichroism and thermal denaturation indicate that the fundamental structural characteristics of wild ..
  20. Caddick S, Muskett F, Stoneman R, Woolfson D. Synthetic ligands for apo-neocarzinostatin. J Am Chem Soc. 2006;128:4204-5 pubmed
    ..This work indicates that apo-Neocarzinostatin has multiple selective and distinct binding modes for small-molecule cargo. ..
  21. Xie J, Burz D, He W, Bronstein I, Lednev I, Shekhtman A. Hexameric calgranulin C (S100A12) binds to the receptor for advanced glycated end products (RAGE) using symmetric hydrophobic target-binding patches. J Biol Chem. 2007;282:4218-31 pubmed
    ..This arrangement creates a large platform for effectively transmitting RAGE-dependent signals from extracellular S100 proteins to the cytoplasmic signaling complexes. ..
  22. Im C, Eberhard S, Huang K, Beck C, Grossman A. Phototropin involvement in the expression of genes encoding chlorophyll and carotenoid biosynthesis enzymes and LHC apoproteins in Chlamydomonas reinhardtii. Plant J. 2006;48:1-16 pubmed
  23. Kansal R, Aziz R, Kotb M. Modulation of expression of superantigens by human transferrin and lactoferrin: a novel mechanism in host-Streptococcus interactions. J Infect Dis. 2005;191:2121-9 pubmed
    ..Thus, ferrins may play an important role in host-pathogen interactions in skin and mucosal tissues. ..
  24. Ruotolo B, Giles K, Campuzano I, Sandercock A, Bateman R, Robinson C. Evidence for macromolecular protein rings in the absence of bulk water. Science. 2005;310:1658-61 pubmed
  25. Adamo A, Paez P, Escobar Cabrera O, Wolfson M, Franco P, Pasquini J, et al. Remyelination after cuprizone-induced demyelination in the rat is stimulated by apotransferrin. Exp Neurol. 2006;198:519-29 pubmed
    ..The results of this study suggest that apotransferrin is a very active promyelinating agent which could be important for the treatment of certain demyelinating conditions. ..
  26. Koglin A, Mofid M, Lohr F, Schäfer B, Rogov V, Blum M, et al. Conformational switches modulate protein interactions in peptide antibiotic synthetases. Science. 2006;312:273-6 pubmed
    ..We further demonstrate that this conformational diversity is an essential prerequisite for the directed movement of the 4'-PP cofactor and its interaction with externally acting proteins such as thioesterases and 4'-PP transferase. ..
  27. Alverdi V, Mazon H, Versluis C, Hemrika W, Esposito G, van den Heuvel R, et al. cGMP-binding prepares PKG for substrate binding by disclosing the C-terminal domain. J Mol Biol. 2008;375:1380-93 pubmed
    ..More surprisingly, our data revealed a specific disclosure of the substrate-binding region of holo-PKG, shedding new light into the kinase-activation process of PKG. ..
  28. Babor M, Gerzon S, Raveh B, Sobolev V, Edelman M. Prediction of transition metal-binding sites from apo protein structures. Proteins. 2008;70:208-17 pubmed
  29. Showalter S, Bruschweiler Li L, Johnson E, Zhang F, Bruschweiler R. Quantitative lid dynamics of MDM2 reveals differential ligand binding modes of the p53-binding cleft. J Am Chem Soc. 2008;130:6472-8 pubmed publisher
    ..The lid dynamics thereby represents a signature for the experimental and virtual screening of therapeutic antagonists that target the p53-MDM2 interaction. ..
  30. Celik L, Lund J, Schiøtt B. Conformational dynamics of the estrogen receptor alpha: molecular dynamics simulations of the influence of binding site structure on protein dynamics. Biochemistry. 2007;46:1743-58 pubmed
    ..Finally, the influence of such conformations on the biological function of ERalpha is discussed in relationship to the interaction with selective estrogen receptor modulators and endocrine-disrupting compounds. ..
  31. Bueno M, Ayuso Tejedor S, Sancho J. Do proteins with similar folds have similar transition state structures? A diffuse transition state of the 169 residue apoflavodoxin. J Mol Biol. 2006;359:813-24 pubmed
    ..The data gathered on the apoflavodoxin transition state are compared with results from experimental studies in other proteins to revisit the relationship between the native state topology and transition state structure. ..
  32. Paez P, Garcia C, Soto E, Pasquini J. Apotransferrin decreases the response of oligodendrocyte progenitors to PDGF and inhibits the progression of the cell cycle. Neurochem Int. 2006;49:359-71 pubmed
    ..The modulation by aTf of the response of OPcs to PDGF supports the idea that this glycoprotein might act as a key regulator of the OLGc lineage progression. ..
  33. Kayatekin C, Zitzewitz J, Matthews C. Zinc binding modulates the entire folding free energy surface of human Cu,Zn superoxide dismutase. J Mol Biol. 2008;384:540-55 pubmed publisher
  34. Heymann J, Weaver K, Mietzner T, Crumbliss A. Sulfate as a synergistic anion facilitating iron binding by the bacterial transferrin FbpA: the origins and effects of anion promiscuity. J Am Chem Soc. 2007;129:9704-12 pubmed
    ..This structural and thermodynamic analysis of anion binding in FeFbpA-X provides additional insight into anion promiscuity and importance. ..
  35. Tang C, Schwieters C, Clore G. Open-to-closed transition in apo maltose-binding protein observed by paramagnetic NMR. Nature. 2007;449:1078-82 pubmed
    ..Using ensemble simulated annealing refinement against the PRE data we are able to determine a <r(-6)> ensemble average structure of the minor apo species and show that it is distinct from the sugar-bound state. ..
  36. Malik S, Revington M, Smith S, Shaw G. Analysis of the structure of human apo-S100B at low temperature indicates a unimodal conformational distribution is adopted by calcium-free S100 proteins. Proteins. 2008;73:28-42 pubmed publisher
    ..This shows that calcium binding to the S100 proteins causes not only a conformational change but results in a tighter distribution of helices within the EF2 calcium binding site required for target protein interactions. ..
  37. Cremades N, Velazquez Campoy A, Freire E, Sancho J. The flavodoxin from Helicobacter pylori: structural determinants of thermostability and FMN cofactor binding. Biochemistry. 2008;47:627-39 pubmed
    ..pylori. Finally, a new strategy is proposed to identify using COREX structural characteristics of equilibrium intermediate states populated during protein unfolding. ..
  38. Jayachithra K, Kumar T, Lu T, Yu C, Chin D. Cold instability of aponeocarzinostatin and its stabilization by labile chromophore. Biophys J. 2005;88:4252-61 pubmed
    ..Interestingly, the labile enediyne chromophore, which is highly stabilized by the protein, is able to protect the protein against cold-induced unfolding, but not the heat-induced unfolding. ..
  39. Frey S, Nagl B, Henze A, Raila J, Schlosser B, Berg T, et al. Isoforms of retinol binding protein 4 (RBP4) are increased in chronic diseases of the kidney but not of the liver. Lipids Health Dis. 2008;7:29 pubmed publisher
    ..The occurrence of RBP4 isoforms is not influenced by liver function but seems to be strongly related to kidney function and may therefore be important in investigating kidney function and related disorders. ..
  40. Iannuzzi C, Vilasi S, Portaccio M, Irace G, Sirangelo I. Heme binding inhibits the fibrillization of amyloidogenic apomyoglobin and determines lack of aggregate cytotoxicity. Protein Sci. 2007;16:507-16 pubmed
    ..These results open new insights into the relationship between the structure adopted by the protein into the aggregates and their ability to trigger the impairment of cell viability. ..
  41. Bueno M, Campos L, Estrada J, Sancho J. Energetics of aliphatic deletions in protein cores. Protein Sci. 2006;15:1858-72 pubmed
    ..In contrast, sequence conservation within the flavodoxin family, which is a good predictor for charge-reversal stabilizing mutations, does not perform so well for aliphatic shortening ones. ..
  42. Bollen Y, Kamphuis M, van Mierlo C. The folding energy landscape of apoflavodoxin is rugged: hydrogen exchange reveals nonproductive misfolded intermediates. Proc Natl Acad Sci U S A. 2006;103:4095-100 pubmed
    ..All PUFs detected thus are off the protein's productive folding route...
  43. Nishimura C, Lietzow M, Dyson H, Wright P. Sequence determinants of a protein folding pathway. J Mol Biol. 2005;351:383-92 pubmed
  44. Bollen Y, van Mierlo C. Protein topology affects the appearance of intermediates during the folding of proteins with a flavodoxin-like fold. Biophys Chem. 2005;114:181-9 pubmed
    ..Apparently, protein topology governs the appearance and kinetic roles of protein folding intermediates during the folding of proteins that have a flavodoxin-like fold. ..
  45. Sudhahar C, Chin D. Aponeocarzinostatin--a superior drug carrier exhibiting unusually high endurance against denaturants. Bioorg Med Chem. 2006;14:3543-52 pubmed
    ..The results highlight the unusual structural stability of aponeocarzinostatin against chemical denaturants, suggesting the potential of aponeocarzinostatin as an inherently superior carrier in drug delivery systems. ..
  46. Golla K, Cherukuvada B, Ahmed F, Kondapi A. Efficacy, safety and anticancer activity of protein nanoparticle-based delivery of doxorubicin through intravenous administration in rats. PLoS ONE. 2012;7:e51960 pubmed publisher
    ..Drug delivery through nanoformulations not only minimizes the cardiotoxicity of doxorubicin but also enhances the efficacy and bioavailability of the drug in a target-specific manner. ..
  47. Liu X, Yang P, Yang W, Yue D. Enzyme-inhibitor-like tuning of Ca(2+) channel connectivity with calmodulin. Nature. 2010;463:968-72 pubmed publisher
    ..Strategies such as ours promise key advances for the in situ analysis of signalling molecules resistant to in vitro reconstitution, such as Ca(2+) channels. ..
  48. Quarles C, Brumaghim J, Marcus R. Simultaneous multiple element detection by particle beam/hollow cathode-optical emission spectroscopy as a tool for metallomic studies: determinations of metal binding with apo-transferrin. Metallomics. 2010;2:154-61 pubmed publisher
    ..Addition of Ag(+) to this mixture does not affect the other metals' distributions, but reflects binding at other protein sites. ..
  49. Sharma H, Yu S, Kong J, Wang J, Steitz T. Structure of apo-CAP reveals that large conformational changes are necessary for DNA binding. Proc Natl Acad Sci U S A. 2009;106:16604-9 pubmed publisher
    ..These interactions are associated with the reorientation and elongation of the C-helices that precludes the formation of the inactive structure. ..
  50. Han W, Sandala G, Giammona D, Bashford D, Noodleman L. Mössbauer properties of the diferric cluster and the differential iron(II)-binding affinity of the iron sites in protein R2 of class Ia Escherichia coli ribonucleotide reductase: a DFT/electrostatics study. Dalton Trans. 2011;40:11164-75 pubmed publisher
    ..Therefore our calculations support the proposal of the previous Mössbauer spectroscopy and two-iron-isotope reaction experiments by Bollinger et al. ..
  51. Bovi M, Cenci L, Perduca M, Capaldi S, Carrizo M, Civiero L, et al. BEL ?-trefoil: a novel lectin with antineoplastic properties in king bolete (Boletus edulis) mushrooms. Glycobiology. 2013;23:578-92 pubmed publisher
    ..No important conformational changes are observed in the lectin when comparing its co-crystals with carbohydrates with those of the ligand-free protein. ..
  52. Zhang C, Gao C, Mu J, Qiu Z, Li L. Spectroscopic studies on unfolding processes of apo-neuroglobin induced by guanidine hydrochloride and urea. Biomed Res Int. 2013;2013:349542 pubmed publisher
    ..The result showed that GdnHCl can efficiently affect the conformational states of apoNgb compared with those of urea. The work will benefit to have an understanding of the unfolding mechanism of apoNgb induced by GdnHCl and urea. ..
  53. Lukacs C, Belunis C, Crowther R, Danho W, Gao L, Goggin B, et al. The structure of XIAP BIR2: understanding the selectivity of the BIR domains. Acta Crystallogr D Biol Crystallogr. 2013;69:1717-25 pubmed publisher