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The structures of RNase A complexed with 3'-CMP and d(CpA): active site conformation and conserved water molecules.

Zegers I, Maes D, Dao-Thi MH, Poortmans F, Palmer R, Wyns L
Protein Sci 3 2322-39 (1994)
Related entries: 1rpf, 1rpg

Cited: 99 times
EuropePMC logo PMID: 7756988

Abstract

The interactions of RNase A with cytidine 3'-monophosphate (3'-CMP) and deoxycytidyl-3',5'-deoxyadenosine (d(CpA)) were analyzed by X-ray crystallography. The 3'-CMP complex and the native structure were determined from trigonal crystals, and the d(CpA) complex from monoclinic crystals. The differences between the overall structures are concentrated in loop regions and are relatively small. The protein-inhibitor contacts are interpreted in terms of the catalytic mechanism. The general base His 12 interacts with the 2' oxygen, as does the electrostatic catalyst Lys 41. The general acid His 119 has 2 conformations (A and B) in the native structure and is found in, respectively, the A and the B conformation in the d(CpA) and the 3'-CMP complex. From the present structures and from a comparison with RNase T1, we propose that His 119 is active in the A conformation. The structure of the d(CpA) complex permits a detailed analysis of the downstream binding site, which includes His 119 and Asn 71. The comparison of the present RNase A structures with an inhibitor complex of RNase T1 shows that there are important similarities in the active sites of these 2 enzymes, despite the absence of any sequence homology. The water molecules were analyzed in order to identify conserved water sites. Seventeen water sites were found to be conserved in RNase A structures from 5 different space groups. It is proposed that 7 of those water molecules play a role in the binding of the N-terminal helix to the rest of the protein and in the stabilization of the active site.

Reviews - 1rph mentioned but not cited (1)

  1. Significance of Histidine Hydrogen-Deuterium Exchange Mass Spectrometry in Protein Structural Biology. Miyagi M, Nakazawa T. Biology (Basel) 13 37 (2024)

Articles - 1rph mentioned but not cited (4)

  1. His...Asp catalytic dyad of ribonuclease A: structure and function of the wild-type, D121N, and D121A enzymes. Schultz LW, Quirk DJ, Raines RT. Biochemistry 37 8886-8898 (1998)
  2. Conformational strictness required for maximum activity and stability of bovine pancreatic ribonuclease A as revealed by crystallographic study of three Phe120 mutants at 1.4 A resolution. Chatani E, Hayashi R, Moriyama H, Ueki T. Protein Sci 11 72-81 (2002)
  3. NMR of hydrogen bonding in cold-shock protein A and an analysis of the influence of crystallographic resolution on comparisons of hydrogen bond lengths. Alexandrescu AT, Snyder DR, Abildgaard F. Protein Sci 10 1856-1868 (2001)
  4. Imidazole C-2 hydrogen/deuterium exchange reaction at histidine for probing protein structure and function with matrix-assisted laser desorption ionization mass spectrometry. Hayashi N, Kuyama H, Nakajima C, Kawahara K, Miyagi M, Nishimura O, Matsuo H, Nakazawa T. Biochemistry 53 1818-1826 (2014)


Reviews citing this publication (6)

  1. A decade of protein engineering on ribonuclease T1--atomic dissection of the enzyme-substrate interactions. Steyaert J. Eur J Biochem 247 1-11 (1997)
  2. Ribozyme catalysis revisited: is water involved? Walter NG. Mol Cell 28 923-929 (2007)
  3. Using NMR spectroscopy to elucidate the role of molecular motions in enzyme function. Lisi GP, Loria JP. Prog Nucl Magn Reson Spectrosc 92-93 1-17 (2016)
  4. Structural and functional importance of local and global conformational fluctuations in the RNase A superfamily. Gagné D, Doucet N. FEBS J 280 5596-5607 (2013)
  5. Nucleotide binding architecture for secreted cytotoxic endoribonucleases. Boix E, Blanco JA, Nogués MV, Moussaoui M. Biochimie 95 1087-1097 (2013)
  6. Integration of kinetic isotope effect analyses to elucidate ribonuclease mechanism. Harris ME, Piccirilli JA, York DM. Biochim Biophys Acta 1854 1801-1808 (2015)

Articles citing this publication (88)

  1. Mechanism of ribonuclease inhibition by ribonuclease inhibitor protein based on the crystal structure of its complex with ribonuclease A. Kobe B, Deisenhofer J. J Mol Biol 264 1028-1043 (1996)
  2. Packing at the protein-water interface. Gerstein M, Chothia C. Proc Natl Acad Sci U S A 93 10167-10172 (1996)
  3. Variability in the pKa of histidine side-chains correlates with burial within proteins. Edgcomb SP, Murphy KP. Proteins 49 1-6 (2002)
  4. The mechanism of rate-limiting motions in enzyme function. Watt ED, Shimada H, Kovrigin EL, Loria JP. Proc Natl Acad Sci U S A 104 11981-11986 (2007)
  5. All in one: a highly detailed rotamer library improves both accuracy and speed in the modelling of sidechains by dead-end elimination. De Maeyer M, Desmet J, Lasters I. Fold Des 2 53-66 (1997)
  6. A critical assessment of comparative molecular modeling of tertiary structures of proteins. Mosimann S, Meleshko R, James MN. Proteins 23 301-317 (1995)
  7. Structural basis of carbohydrate recognition by the lectin LecB from Pseudomonas aeruginosa. Loris R, Tielker D, Jaeger KE, Wyns L. J Mol Biol 331 861-870 (2003)
  8. The flexibility of a distant loop modulates active site motion and product release in ribonuclease A. Doucet N, Watt ED, Loria JP. Biochemistry 48 7160-7168 (2009)
  9. Analysis of the mechanism of the Serratia nuclease using site-directed mutagenesis. Friedhoff P, Kolmes B, Gimadutdinow O, Wende W, Krause KL, Pingoud A. Nucleic Acids Res 24 2632-2639 (1996)
  10. Protein titration in the crystal state. Berisio R, Lamzin VS, Sica F, Wilson KS, Zagari A, Mazzarella L. J Mol Biol 292 845-854 (1999)
  11. Experimental and computational analysis of the transition state for ribonuclease A-catalyzed RNA 2'-O-transphosphorylation. Gu H, Zhang S, Wong KY, Radak BK, Dissanayake T, Kellerman DL, Dai Q, Miyagi M, Anderson VE, York DM, Piccirilli JA, Harris ME. Proc Natl Acad Sci U S A 110 13002-13007 (2013)
  12. Conserved water molecules contribute to the extensive network of interactions at the active site of protein kinase A. Shaltiel S, Cox S, Taylor SS. Proc Natl Acad Sci U S A 95 484-491 (1998)
  13. The structure of the endoribonuclease XendoU: From small nucleolar RNA processing to severe acute respiratory syndrome coronavirus replication. Renzi F, Caffarelli E, Laneve P, Bozzoni I, Brunori M, Vallone B. Proc Natl Acad Sci U S A 103 12365-12370 (2006)
  14. The three-dimensional structure of human RNase 4, unliganded and complexed with d(Up), reveals the basis for its uridine selectivity. Terzyan SS, Peracaula R, de Llorens R, Tsushima Y, Yamada H, Seno M, Gomis-Rüth FX, Coll M. J Mol Biol 285 205-214 (1999)
  15. Interaction of human pancreatic ribonuclease with human ribonuclease inhibitor. Generation of inhibitor-resistant cytotoxic variants. Gaur D, Swaminathan S, Batra JK. J Biol Chem 276 24978-24984 (2001)
  16. Three-dimensional crystal structure of human eosinophil cationic protein (RNase 3) at 1.75 A resolution. Mallorquí-Fernández G, Pous J, Peracaula R, Aymamí J, Maeda T, Tada H, Yamada H, Seno M, de Llorens R, Gomis-Rüth FX, Coll M. J Mol Biol 300 1297-1307 (2000)
  17. Reversible substrate-induced domain motions in ribonuclease A. Vitagliano L, Merlino A, Zagari A, Mazzarella L. Proteins 46 97-104 (2002)
  18. Dynamic properties of the N-terminal swapped dimer of ribonuclease A. Merlino A, Vitagliano L, Ceruso MA, Mazzarella L. Biophys J 86 2383-2391 (2004)
  19. Crystallographic analysis of human immunodeficiency virus 1 protease with an analog of the conserved CA-p2 substrate -- interactions with frequently occurring glutamic acid residue at P2' position of substrates. Weber IT, Wu J, Adomat J, Harrison RW, Kimmel AR, Wondrak EM, Louis JM. Eur J Biochem 249 523-530 (1997)
  20. Productive and nonproductive binding to ribonuclease A: X-ray structure of two complexes with uridylyl(2',5')guanosine. Vitagliano L, Merlino A, Zagari A, Mazzarella L. Protein Sci 9 1217-1225 (2000)
  21. Conserved water molecules in a large family of microbial ribonucleases. Loris R, Langhorst U, De Vos S, Decanniere K, Bouckaert J, Maes D, Transue TR, Steyaert J. Proteins 36 117-134 (1999)
  22. Global and local motions in ribonuclease A: a molecular dynamics study. Merlino A, Vitagliano L, Ceruso MA, Di Nola A, Mazzarella L. Biopolymers 65 274-283 (2002)
  23. Three-dimensional solution structure of human angiogenin determined by 1H,15N-NMR spectroscopy--characterization of histidine protonation states and pKa values. Lequin O, Thüring H, Robin M, Lallemand JY. Eur J Biochem 250 712-726 (1997)
  24. Sequence-specific artificial ribonucleases. I. Bis-imidazole-containing oligonucleotide conjugates prepared using precursor-based strategy. Beloglazova NG, Fabani MM, Zenkova MA, Bichenkova EV, Polushin NN, Sil'nikov VV, Douglas KT, Vlassov VV. Nucleic Acids Res 32 3887-3897 (2004)
  25. DRoP: a water analysis program identifies Ras-GTP-specific pathway of communication between membrane-interacting regions and the active site. Kearney BM, Johnson CW, Roberts DM, Swartz P, Mattos C. J Mol Biol 426 611-629 (2014)
  26. Structure and stability of the non-covalent swapped dimer of bovine seminal ribonuclease: an enzyme tailored to evade ribonuclease protein inhibitor. Sica F, Di Fiore A, Merlino A, Mazzarella L. J Biol Chem 279 36753-36760 (2004)
  27. Molecular mechanics analysis of drug-resistant mutants of HIV protease. Weber IT, Harrison RW. Protein Eng 12 469-474 (1999)
  28. Two crystal structures of the leupeptin-trypsin complex. Kurinov IV, Harrison RW. Protein Sci 5 752-758 (1996)
  29. Binding of a substrate analog to a domain swapping protein: X-ray structure of the complex of bovine seminal ribonuclease with uridylyl(2',5')adenosine. Vitagliano L, Adinolfi S, Riccio A, Sica F, Zagari A, Mazzarella L. Protein Sci 7 1691-1699 (1998)
  30. Enzymatic and structural characterisation of amphinase, a novel cytotoxic ribonuclease from Rana pipiens oocytes. Singh UP, Ardelt W, Saxena SK, Holloway DE, Vidunas E, Lee HS, Saxena A, Shogen K, Acharya KR. J Mol Biol 371 93-111 (2007)
  31. Interpretation of pH-activity profiles for acid-base catalysis from molecular simulations. Dissanayake T, Swails JM, Harris ME, Roitberg AE, York DM. Biochemistry 54 1307-1313 (2015)
  32. Multiple solvent crystal structures of ribonuclease A: an assessment of the method. Dechene M, Wink G, Smith M, Swartz P, Mattos C. Proteins 76 861-881 (2009)
  33. Analysis of six protein structures predicted by comparative modeling techniques. Harrison RW, Chatterjee D, Weber IT. Proteins 23 463-471 (1995)
  34. Hydrophobic collapse in (in silico) protein folding. Brylinski M, Konieczny L, Roterman I. Comput Biol Chem 30 255-267 (2006)
  35. The solution structure of a cytotoxic ribonuclease from the oocytes of Rana catesbeiana (bullfrog). Chang CF, Chen C, Chen YC, Hom K, Huang RF, Huang TH. J Mol Biol 283 231-244 (1998)
  36. Three-dimensional structure of the complexes of ribonuclease A with 2',5'-CpA and 3',5'-d(CpA) in aqueous solution, as obtained by NMR and restrained molecular dynamics. Toiron C, González C, Bruix M, Rico M. Protein Sci 5 1633-1647 (1996)
  37. Molecular mechanics calculations on Rous sarcoma virus protease with peptide substrates. Weber IT, Harrison RW. Protein Sci 6 2365-2374 (1997)
  38. The binding of 3'-N-piperidine-4-carboxyl-3'-deoxy-ara-uridine to ribonuclease A in the crystal. Leonidas DD, Maiti TK, Samanta A, Dasgupta S, Pathak T, Zographos SE, Oikonomakos NG. Bioorg Med Chem 14 6055-6064 (2006)
  39. 5'-Diphosphoadenosine 3'-phosphate is a potent inhibitor of bovine pancreatic ribonuclease A. Russo N, Shapiro R, Vallee BL. Biochem Biophys Res Commun 231 671-674 (1997)
  40. Molecular dynamics simulation of bovine pancreatic ribonuclease A-CpA and transition state-like complexes. Formoso E, Matxain JM, Lopez X, York DM. J Phys Chem B 114 7371-7382 (2010)
  41. Ribonuclease A homologues of the zebrafish: polymorphism, crystal structures of two representatives and their evolutionary implications. Kazakou K, Holloway DE, Prior SH, Subramanian V, Acharya KR. J Mol Biol 380 206-222 (2008)
  42. The first crystal structure of human RNase 6 reveals a novel substrate-binding and cleavage site arrangement. Prats-Ejarque G, Arranz-Trullén J, Blanco JA, Pulido D, Nogués MV, Moussaoui M, Boix E. Biochem J 473 1523-1536 (2016)
  43. Population shift vs induced fit: the case of bovine seminal ribonuclease swapping dimer. Merlino A, Vitagliano L, Sica F, Zagari A, Mazzarella L. Biopolymers 73 689-695 (2004)
  44. Polyamine derivatives as selective RNaseA mimics. Fouace S, Gaudin C, Picard S, Corvaisier S, Renault J, Carboni B, Felden B. Nucleic Acids Res 32 151-157 (2004)
  45. Structure and stability of the P93G variant of ribonuclease A. Schultz LW, Hargraves SR, Klink TA, Raines RT. Protein Sci 7 1620-1625 (1998)
  46. Ribonuclease A mutant His119 Asn: the role of histidine in catalysis. Panov KI, Kolbanovskaya EY, Okorokov AL, Panova TB, Terwisscha van Scheltinga AC, Karpeisky MYa, Beintema JJ. FEBS Lett 398 57-60 (1996)
  47. The unswapped chain of bovine seminal ribonuclease: Crystal structure of the free and liganded monomeric derivative. Sica F, Di Fiore A, Zagari A, Mazzarella L. Proteins 52 263-271 (2003)
  48. A catalytic function for the structurally conserved residue Phe 100 of ribonuclease T1. Doumen J, Gonciarz M, Zegers I, Loris R, Wyns L, Steyaert J. Protein Sci 5 1523-1530 (1996)
  49. Characterization of disulfide bonds by planned digestion and tandem mass spectrometry. Na S, Paek E, Choi JS, Kim D, Lee SJ, Kwon J. Mol Biosyst 11 1156-1164 (2015)
  50. Crystal structures of the copper and nickel complexes of RNase A: metal-induced interprotein interactions and identification of a novel copper binding motif. Balakrishnan R, Ramasubbu N, Varughese KI, Parthasarathy R. Proc Natl Acad Sci U S A 94 9620-9625 (1997)
  51. Structure of murine angiogenin: features of the substrate- and cell-binding regions and prospects for inhibitor-binding studies. Holloway DE, Chavali GB, Hares MC, Subramanian V, Acharya KR. Acta Crystallogr D Biol Crystallogr 61 1568-1578 (2005)
  52. Crystal structure of Onconase at 1.1 Å resolution--insights into substrate binding and collective motion. Holloway DE, Singh UP, Shogen K, Acharya KR. FEBS J 278 4136-4149 (2011)
  53. Evolutionary Trends in RNA Base Selectivity Within the RNase A Superfamily. Prats-Ejarque G, Lu L, Salazar VA, Moussaoui M, Boix E. Front Pharmacol 10 1170 (2019)
  54. The crystal structure of ribonuclease A in complex with thymidine-3'-monophosphate provides further insight into ligand binding. Doucet N, Jayasundera TB, Simonović M, Loria JP. Proteins 78 2459-2468 (2010)
  55. Crystal structures of murine angiogenin-2 and -3-probing 'structure--function' relationships amongst angiogenin homologues. Iyer S, Holloway DE, Acharya KR. FEBS J 280 302-318 (2013)
  56. Effect of deamidation on folding of ribonuclease A. Orrù S, Vitagliano L, Esposito L, Mazzarella L, Marino G, Ruoppolo M. Protein Sci 9 2577-2582 (2000)
  57. Influence of naturally-occurring 5'-pyrophosphate-linked substituents on the binding of adenylic inhibitors to ribonuclease a: an X-ray crystallographic study. Holloway DE, Chavali GB, Leonidas DD, Baker MD, Acharya KR. Biopolymers 91 995-1008 (2009)
  58. Nucleoside-amino acid conjugates: An alternative route to the design of ribonuclease A inhibitors. Debnath J, Dasgupta S, Pathak T. Bioorg Med Chem 17 4921-4927 (2009)
  59. The binding of IMP to ribonuclease A. Hatzopoulos GN, Leonidas DD, Kardakaris R, Kobe J, Oikonomakos NG. FEBS J 272 3988-4001 (2005)
  60. A Multidimensional B-Spline Correction for Accurate Modeling Sugar Puckering in QM/MM Simulations. Huang M, Dissanayake T, Kuechler E, Radak BK, Lee TS, Giese TJ, York DM. J Chem Theory Comput 13 3975-3984 (2017)
  61. Functional and structural analyses of N-acylsulfonamide-linked dinucleoside inhibitors of RNase A. Thiyagarajan N, Smith BD, Raines RT, Acharya KR. FEBS J 278 541-549 (2011)
  62. Deducing hydration sites of a protein from molecular dynamics simulations. Madhusudhan MS, Vishveshwara S. J Biomol Struct Dyn 19 105-114 (2001)
  63. Recognition of ribonuclease A by 3'-5'-pyrophosphate-linked dinucleotide inhibitors: a molecular dynamics/continuum electrostatics analysis. Polydoridis S, Leonidas DD, Oikonomakos NG, Archontis G. Biophys J 92 1659-1672 (2007)
  64. The Lepidopteran endoribonuclease-U domain protein P102 displays dramatically reduced enzymatic activity and forms functional amyloids. Pascale M, Laurino S, Vogel H, Grimaldi A, Monné M, Riviello L, Tettamanti G, Falabella P. Dev Comp Immunol 47 129-139 (2014)
  65. Bridging solvent molecules mediate RNase A - Ligand binding. Ivanov SM, Dimitrov I, Doytchinova IA. PLoS One 14 e0224271 (2019)
  66. Comparison of the dynamics of bovine and human angiogenin: a molecular dynamics study. Madhusudhan MS, Vishveshwara S. Biopolymers 49 131-144 (1999)
  67. Computer modeling of human angiogenin-dinucleotide substrate interaction. Madhusudhan MS, Vishveshwara S. Proteins 42 125-135 (2001)
  68. Replacement of His12 or His119 of bovine pancreatic ribonuclease A with acidic amino acid residues for the modification of activity and stability. Tanimizu N, Ueno H, Hayashi R. J Biosci Bioeng 94 39-44 (2002)
  69. Spectroscopic/Computational Characterization and the X-ray Structure of the Adduct of the VIVO-Picolinato Complex with RNase A. Ferraro G, Demitri N, Vitale L, Sciortino G, Sanna D, Ugone V, Garribba E, Merlino A. Inorg Chem 60 19098-19109 (2021)
  70. Crystallographic and functional studies of a modified form of eosinophil-derived neurotoxin (EDN) with novel biological activities. Chang C, Newton DL, Rybak SM, Wlodawer A. J Mol Biol 317 119-130 (2002)
  71. Modeling of angiogenin - 3-NMP complex. Madhusudhan MS, Vishveshwara S. J Biomol Struct Dyn 16 715-722 (1998)
  72. Ternary borate-nucleoside complex stabilization by ribonuclease A demonstrates phosphate mimicry. Gabel SA, London RE. J Biol Inorg Chem 13 207-217 (2008)
  73. Atomic hydration potentials using a Monte Carlo Reference State (MCRS) for protein solvation modeling. Rakhmanov SV, Makeev VJ. BMC Struct Biol 7 19 (2007)
  74. Sequence-specific backbone (1)H, (13)C, and (15)N resonance assignments of human ribonuclease 4. Gagné D, Doucet N. Biomol NMR Assign 9 181-185 (2015)
  75. Water clusters in life. Lo SY, Li WC, Huang SH. Med Hypotheses 54 948-953 (2000)
  76. A new crystal form of bovine pancreatic RNase A in complex with 2'-deoxyguanosine-5'-monophosphate. Larson SB, Day JS, Cudney R, McPherson A. Acta Crystallogr Sect F Struct Biol Cryst Commun 63 728-733 (2007)
  77. Tautomeric stabilities of 4-fluorohistidine shed new light on mechanistic experiments with labeled ribonuclease A. Kasireddy C, Ellis JM, Bann JG, Mitchell-Koch KR. Chem Phys Lett 666 58-61 (2016)
  78. Ab initio study of the reaction mechanism of ribonuclease A with cytidyl-3',5'-adenosine. I. Geometry optimization of cytidyl-3', 5'-adenosine. Peeters A, Van Alsenoy C. Biopolymers 50 697-704 (1999)
  79. Chemical synthesis and enzymatic properties of RNase A analogues designed to enhance second-step catalytic activity. Boerema DJ, Tereshko VA, Zhang J, Kent SB. Org Biomol Chem 14 8804-8814 (2016)
  80. Conformation of 3'CMP bound to RNase A using TrNOESY. Lee YC, Jackson PL, Jablonsky MJ, Muccio DD. Arch Biochem Biophys 463 37-46 (2007)
  81. Exploring the RNase A scaffold to combine catalytic and antimicrobial activities. Structural characterization of RNase 3/1 chimeras. Fernández-Millán P, Vázquez-Monteagudo S, Boix E, Prats-Ejarque G. Front Mol Biosci 9 964717 (2022)
  82. Ligand-protein target screening from cell matrices using reactive desorption electrospray ionization-mass spectrometry via a native-denatured exchange approach. Zheng Q, Ruan X, Tian Y, Hu J, Wan N, Lu W, Xu X, Wang G, Hao H, Ye H. Analyst 144 512-520 (2019)
  83. Nucleotide docking: prediction of reactant state complexes for ribonuclease enzymes. Elsässer B, Fels G. J Mol Model 17 1953-1962 (2011)
  84. RNA Cleavage Properties of Nucleobase-Specific RNase MC1 and Cusativin Are Determined by the Dinucleotide-Binding Interactions in the Enzyme-Active Site. Thakur P, Atway J, Limbach PA, Addepalli B. Int J Mol Sci 23 7021 (2022)
  85. Site-selective artificial ribonucleases: oligonucleotide conjugates containing multiple imidazole residues in the catalytic domain. Beloglazova NG, Fabani MM, Polushin NN, Sil'nikov VV, Vlassov VV, Bichenkova EV, Zenkova MA. J Nucleic Acids 2011 748632 (2011)
  86. Ultra-high resolution X-ray structure of orthorhombic bovine pancreatic Ribonuclease A at 100K. Lisgarten DR, Palmer RA, Cooper JB, Naylor CE, Talbert RC, Howlin BJ, Lisgarten JN, Konc J, Najmudin S, Lobley CMC. BMC Chem 17 91 (2023)
  87. An insight into the ribonucleolytic and antiangiogenic activity of buffalo lactoferrin. Tripathy DR, Pandey NK, Dinda AK, Ghosh S, Singha Roy A, Dasgupta S. J Biomol Struct Dyn 33 184-195 (2015)
  88. RNase-stable RNA: conformational parameters of the nucleic acid backbone for binding to RNase T1. Greiner-Stöffele T, Förster HH, Hofmann HJ, Hahn U. Biol Chem 382 1007-1017 (2001)


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