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. 2000 Mar;78(3):1541–1550. doi: 10.1016/S0006-3495(00)76706-3

Induced fit in arginine kinase.

G Zhou 1, W R Ellington 1, M S Chapman 1
PMCID: PMC1300751  PMID: 10692338

Abstract

Creatine kinase (CK) and arginine kinase (AK) are related enzymes that reversibly transfer a phosphoryl group between a guanidino compound and ADP. In the buffering of ATP energy levels, they are central to energy metabolism and have been paradigms of classical enzymology. Comparison of the open substrate-free structure of CK and the closed substrate-bound structure of AK reveals differences that are consistent with prior biophysical evidence of substrate-induced conformational changes. Large and small domains undergo a hinged 13 degrees rotation. Several loops become ordered and adopt different positions in the presence of substrate, including one (residues 309-319) that moves 15 A to fold over the substrates. The conformational changes appear to be necessary in aligning the two substrates for catalysis, in configuring the active site only when productive phosphoryl transfer is possible, and excluding water from the active site to avoid wasteful ATP hydrolysis.

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Selected References

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  1. Alber T. C., Davenport R. C., Jr, Giammona D. A., Lolis E., Petsko G. A., Ringe D. Crystallography and site-directed mutagenesis of yeast triosephosphate isomerase: what can we learn about catalysis from a "simple" enzyme? Cold Spring Harb Symp Quant Biol. 1987;52:603–613. doi: 10.1101/sqb.1987.052.01.069. [DOI] [PubMed] [Google Scholar]
  2. Anderson C. M., Zucker F. H., Steitz T. A. Space-filling models of kinase clefts and conformation changes. Science. 1979 Apr 27;204(4391):375–380. doi: 10.1126/science.220706. [DOI] [PubMed] [Google Scholar]
  3. Bennett W. S., Jr, Steitz T. A. Structure of a complex between yeast hexokinase A and glucose. II. Detailed comparisons of conformation and active site configuration with the native hexokinase B monomer and dimer. J Mol Biol. 1980 Jun 25;140(2):211–230. doi: 10.1016/0022-2836(80)90103-5. [DOI] [PubMed] [Google Scholar]
  4. Blethen S. L. Kinetic properties of the arginine kinase isoenzymes of Limulus polyphemus. Arch Biochem Biophys. 1972 Mar;149(1):244–251. doi: 10.1016/0003-9861(72)90319-0. [DOI] [PubMed] [Google Scholar]
  5. Connolly M. L. Solvent-accessible surfaces of proteins and nucleic acids. Science. 1983 Aug 19;221(4612):709–713. doi: 10.1126/science.6879170. [DOI] [PubMed] [Google Scholar]
  6. Dafforn A., Koshland D. E., Jr Theoretical aspects of orbital steering. Proc Natl Acad Sci U S A. 1971 Oct;68(10):2463–2467. doi: 10.1073/pnas.68.10.2463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dumas C., Camonis J. Cloning and sequence analysis of the cDNA for arginine kinase of lobster muscle. J Biol Chem. 1993 Oct 15;268(29):21599–21605. [PubMed] [Google Scholar]
  8. Eisenberg D., McLachlan A. D. Solvation energy in protein folding and binding. Nature. 1986 Jan 16;319(6050):199–203. doi: 10.1038/319199a0. [DOI] [PubMed] [Google Scholar]
  9. Forstner M., Kriechbaum M., Laggner P., Wallimann T. Structural changes of creatine kinase upon substrate binding. Biophys J. 1998 Aug;75(2):1016–1023. doi: 10.1016/S0006-3495(98)77590-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fritz-Wolf K., Schnyder T., Wallimann T., Kabsch W. Structure of mitochondrial creatine kinase. Nature. 1996 May 23;381(6580):341–345. doi: 10.1038/381341a0. [DOI] [PubMed] [Google Scholar]
  11. Gerstein M., Chothia C. Analysis of protein loop closure. Two types of hinges produce one motion in lactate dehydrogenase. J Mol Biol. 1991 Jul 5;220(1):133–149. doi: 10.1016/0022-2836(91)90387-l. [DOI] [PubMed] [Google Scholar]
  12. Gerstein M., Krebs W. A database of macromolecular motions. Nucleic Acids Res. 1998 Sep 15;26(18):4280–4290. doi: 10.1093/nar/26.18.4280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gerstein M., Lesk A. M., Chothia C. Structural mechanisms for domain movements in proteins. Biochemistry. 1994 Jun 7;33(22):6739–6749. doi: 10.1021/bi00188a001. [DOI] [PubMed] [Google Scholar]
  14. Gross M., Furter-Graves E. M., Wallimann T., Eppenberger H. M., Furter R. The tryptophan residues of mitochondrial creatine kinase: roles of Trp-223, Trp-206, and Trp-264 in active-site and quaternary structure formation. Protein Sci. 1994 Jul;3(7):1058–1068. doi: 10.1002/pro.5560030708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gross M., Wallimann T. Dimer-dimer interactions in octameric mitochondrial creatine kinase. Biochemistry. 1995 May 23;34(20):6660–6667. doi: 10.1021/bi00020a011. [DOI] [PubMed] [Google Scholar]
  16. Hansen D. E., Knowles J. R. The stereochemical course of the reaction catalyzed by creatine kinase. J Biol Chem. 1981 Jun 25;256(12):5967–5969. [PubMed] [Google Scholar]
  17. Henikoff S., Henikoff J. G. Amino acid substitution matrices from protein blocks. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10915–10919. doi: 10.1073/pnas.89.22.10915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jencks W. P., Page M. I. "Orbital steering", entropy, and rate accelerations. Biochem Biophys Res Commun. 1974 Apr 8;57(3):887–892. doi: 10.1016/0006-291x(74)90629-9. [DOI] [PubMed] [Google Scholar]
  19. Joseph D., Petsko G. A., Karplus M. Anatomy of a conformational change: hinged "lid" motion of the triosephosphate isomerase loop. Science. 1990 Sep 21;249(4975):1425–1428. doi: 10.1126/science.2402636. [DOI] [PubMed] [Google Scholar]
  20. Kabsch W., Fritz-Wolf K. Mitochondrial creatine kinase--a square protein. Curr Opin Struct Biol. 1997 Dec;7(6):811–818. doi: 10.1016/s0959-440x(97)80151-0. [DOI] [PubMed] [Google Scholar]
  21. Kenyon G. L., Reed G. H. Creatine kinase: structure-activity relationships. Adv Enzymol Relat Areas Mol Biol. 1983;54:367–426. doi: 10.1002/9780470122990.ch6. [DOI] [PubMed] [Google Scholar]
  22. Koshland D. E. Application of a Theory of Enzyme Specificity to Protein Synthesis. Proc Natl Acad Sci U S A. 1958 Feb;44(2):98–104. doi: 10.1073/pnas.44.2.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lui N. S., Cunningham L. Cooperative effects of substrates and substrate analogs on the conformation of creatine phosphokinase. Biochemistry. 1966 Jan;5(1):144–149. doi: 10.1021/bi00865a019. [DOI] [PubMed] [Google Scholar]
  24. McDonald R. C., Steitz T. A., Engelman D. M. Yeast hexokinase in solution exhibits a large conformational change upon binding glucose or glucose 6-phosphate. Biochemistry. 1979 Jan 23;18(2):338–342. doi: 10.1021/bi00569a017. [DOI] [PubMed] [Google Scholar]
  25. Mühlebach S. M., Gross M., Wirz T., Wallimann T., Perriard J. C., Wyss M. Sequence homology and structure predictions of the creatine kinase isoenzymes. Mol Cell Biochem. 1994 Apr-May;133-134:245–262. doi: 10.1007/BF01267958. [DOI] [PubMed] [Google Scholar]
  26. Page M. I., Jencks W. P. Entropic contributions to rate accelerations in enzymic and intramolecular reactions and the chelate effect. Proc Natl Acad Sci U S A. 1971 Aug;68(8):1678–1683. doi: 10.1073/pnas.68.8.1678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pai E. F., Sachsenheimer W., Schirmer R. H., Schulz G. E. Substrate positions and induced-fit in crystalline adenylate kinase. J Mol Biol. 1977 Jul;114(1):37–45. doi: 10.1016/0022-2836(77)90281-9. [DOI] [PubMed] [Google Scholar]
  28. Rao B. D., Buttlaire D. H., Cohn M. 31P NMR studies of the arginine kinase reaction. Equilibrium constants and exchange rates at stoichiometric enzyme concentration. J Biol Chem. 1976 Nov 25;251(22):6981–6986. [PubMed] [Google Scholar]
  29. Rao J. K., Bujacz G., Wlodawer A. Crystal structure of rabbit muscle creatine kinase. FEBS Lett. 1998 Nov 13;439(1-2):133–137. doi: 10.1016/s0014-5793(98)01355-6. [DOI] [PubMed] [Google Scholar]
  30. Reed G. H., Cohn M. Structural changes induced by substrates and anions at the active site of creatine kinase. Electron paramagnetic resonance and nuclear magnetic relaxation rate studies of the manganous complexes. J Biol Chem. 1972 May 25;247(10):3073–3081. [PubMed] [Google Scholar]
  31. Rhee S., Parris K. D., Hyde C. C., Ahmed S. A., Miles E. W., Davies D. R. Crystal structures of a mutant (betaK87T) tryptophan synthase alpha2beta2 complex with ligands bound to the active sites of the alpha- and beta-subunits reveal ligand-induced conformational changes. Biochemistry. 1997 Jun 24;36(25):7664–7680. doi: 10.1021/bi9700429. [DOI] [PubMed] [Google Scholar]
  32. Rojo M., Hovius R., Demel R. A., Nicolay K., Wallimann T. Mitochondrial creatine kinase mediates contact formation between mitochondrial membranes. J Biol Chem. 1991 Oct 25;266(30):20290–20295. [PubMed] [Google Scholar]
  33. Schreuder H. A., Knight S., Curmi P. M., Andersson I., Cascio D., Brändén C. I., Eisenberg D. Formation of the active site of ribulose-1,5-bisphosphate carboxylase/oxygenase by a disorder-order transition from the unactivated to the activated form. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9968–9972. doi: 10.1073/pnas.90.21.9968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schubert H. L., Fauman E. B., Stuckey J. A., Dixon J. E., Saper M. A. A ligand-induced conformational change in the Yersinia protein tyrosine phosphatase. Protein Sci. 1995 Sep;4(9):1904–1913. doi: 10.1002/pro.5560040924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schumacher M. A., Carter D., Roos D. S., Ullman B., Brennan R. G. Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop. Nat Struct Biol. 1996 Oct;3(10):881–887. doi: 10.1038/nsb1096-881. [DOI] [PubMed] [Google Scholar]
  36. Stein L. D., Harn D. A., David J. R. A cloned ATP:guanidino kinase in the trematode Schistosoma mansoni has a novel duplicated structure. J Biol Chem. 1990 Apr 25;265(12):6582–6588. [PubMed] [Google Scholar]
  37. Strong S. J., Ellington W. R. Isolation and sequence analysis of the gene for arginine kinase from the chelicerate arthropod, Limulus polyphemus: insights into catalytically important residues. Biochim Biophys Acta. 1995 Jan 19;1246(2):197–200. doi: 10.1016/0167-4838(94)00218-6. [DOI] [PubMed] [Google Scholar]
  38. Stroud R. M. Balancing ATP in the cell. Nat Struct Biol. 1996 Jul;3(7):567–569. doi: 10.1038/nsb0796-567. [DOI] [PubMed] [Google Scholar]
  39. Suzuki T., Furukohri T. Evolution of phosphagen kinase. Primary structure of glycocyamine kinase and arginine kinase from invertebrates. J Mol Biol. 1994 Apr 1;237(3):353–357. doi: 10.1006/jmbi.1994.1237. [DOI] [PubMed] [Google Scholar]
  40. Suzuki T., Kawasaki Y., Furukohri T., Ellington W. R. Evolution of phosphagen kinase. VI. Isolation, characterization and cDNA-derived amino acid sequence of lombricine kinase from the earthworm Eisenia foetida, and identification of a possible candidate for the guanidine substrate recognition site. Biochim Biophys Acta. 1997 Dec 5;1343(2):152–159. doi: 10.1016/s0167-4838(97)00128-3. [DOI] [PubMed] [Google Scholar]
  41. Suzuki T., Kawasaki Y., Furukohri T. Evolution of phosphagen kinase. Isolation, characterization and cDNA-derived amino acid sequence of two-domain arginine kinase from the sea anemone Anthopleura japonicus. Biochem J. 1997 Nov 15;328(Pt 1):301–306. doi: 10.1042/bj3280301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wallimann T., Wyss M., Brdiczka D., Nicolay K., Eppenberger H. M. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis. Biochem J. 1992 Jan 1;281(Pt 1):21–40. doi: 10.1042/bj2810021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wothe D. D., Charbonneau H., Shapiro B. M. The phosphocreatine shuttle of sea urchin sperm: flagellar creatine kinase resulted from a gene triplication. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5203–5207. doi: 10.1073/pnas.87.13.5203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Xie Q., Chapman M. S. Canine parvovirus capsid structure, analyzed at 2.9 A resolution. J Mol Biol. 1996 Dec 6;264(3):497–520. doi: 10.1006/jmbi.1996.0657. [DOI] [PubMed] [Google Scholar]
  45. Zhou G., Somasundaram T., Blanc E., Chen Z., Chapman M. S. Critical initial real-space refinement in the structure determination of arginine kinase. Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):835–845. doi: 10.1107/s0907444999000888. [DOI] [PubMed] [Google Scholar]
  46. Zhou G., Somasundaram T., Blanc E., Parthasarathy G., Ellington W. R., Chapman M. S. Transition state structure of arginine kinase: implications for catalysis of bimolecular reactions. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8449–8454. doi: 10.1073/pnas.95.15.8449. [DOI] [PMC free article] [PubMed] [Google Scholar]

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