Skip to main content
NCBI home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1998 May;7(5):1136–1146. doi: 10.1002/pro.5560070507

Two "unrelated" families of ATP-dependent enzymes share extensive structural similarities about their cofactor binding sites.

K A Denessiouk 1, J V Lehtonen 1, T Korpela 1, M S Johnson 1
PMCID: PMC2144019  PMID: 9605318

Abstract

Two proteins, D-alanine:D-alanine ligase and cAMP-dependent protein kinase, share a remarkable degree of structural convergence despite having different three-dimensional folds and different enzymatic functions. Here we report that as many as 103 residues from 10 segments form two identical super-secondary structures between which the cofactor ATP is bound. The cofactor, two bound metal cations, and several water molecules form a large network of electrostatic and hydrophobic interactions common to both enzymes, and these are mediated by the similar placement of equivalent amino acids within the common supersecondary structures.

Full Text

The Full Text of this article is available as a PDF (7.0 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  2. Bossemeyer D., Engh R. A., Kinzel V., Ponstingl H., Huber R. Phosphotransferase and substrate binding mechanism of the cAMP-dependent protein kinase catalytic subunit from porcine heart as deduced from the 2.0 A structure of the complex with Mn2+ adenylyl imidodiphosphate and inhibitor peptide PKI(5-24). EMBO J. 1993 Mar;12(3):849–859. doi: 10.1002/j.1460-2075.1993.tb05725.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chrivia J. C., Uhler M. D., McKnight G. S. Characterization of genomic clones coding for the C alpha and C beta subunits of mouse cAMP-dependent protein kinase. J Biol Chem. 1988 Apr 25;263(12):5739–5744. [PubMed] [Google Scholar]
  4. De Bondt H. L., Rosenblatt J., Jancarik J., Jones H. D., Morgan D. O., Kim S. H. Crystal structure of cyclin-dependent kinase 2. Nature. 1993 Jun 17;363(6430):595–602. doi: 10.1038/363595a0. [DOI] [PubMed] [Google Scholar]
  5. Fan C., Moews P. C., Walsh C. T., Knox J. R. Vancomycin resistance: structure of D-alanine:D-alanine ligase at 2.3 A resolution. Science. 1994 Oct 21;266(5184):439–443. doi: 10.1126/science.7939684. [DOI] [PubMed] [Google Scholar]
  6. Fan C., Park I. S., Walsh C. T., Knox J. R. D-alanine:D-alanine ligase: phosphonate and phosphinate intermediates with wild type and the Y216F mutant. Biochemistry. 1997 Mar 4;36(9):2531–2538. doi: 10.1021/bi962431t. [DOI] [PubMed] [Google Scholar]
  7. Herzberg O., Chen C. C., Kapadia G., McGuire M., Carroll L. J., Noh S. J., Dunaway-Mariano D. Swiveling-domain mechanism for enzymatic phosphotransfer between remote reaction sites. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2652–2657. doi: 10.1073/pnas.93.7.2652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hubbard S. R., Wei L., Ellis L., Hendrickson W. A. Crystal structure of the tyrosine kinase domain of the human insulin receptor. Nature. 1994 Dec 22;372(6508):746–754. doi: 10.1038/372746a0. [DOI] [PubMed] [Google Scholar]
  9. Matsuda K., Mizuguchi K., Nishioka T., Kato H., Go N., Oda J. Crystal structure of glutathione synthetase at optimal pH: domain architecture and structural similarity with other proteins. Protein Eng. 1996 Dec;9(12):1083–1092. doi: 10.1093/protein/9.12.1083. [DOI] [PubMed] [Google Scholar]
  10. May A. C., Johnson M. S. Improved genetic algorithm-based protein structure comparisons: pairwise and multiple superpositions. Protein Eng. 1995 Sep;8(9):873–882. doi: 10.1093/protein/8.9.873. [DOI] [PubMed] [Google Scholar]
  11. May A. C., Johnson M. S. Protein structure comparisons using a combination of a genetic algorithm, dynamic programming and least-squares minimization. Protein Eng. 1994 Apr;7(4):475–485. doi: 10.1093/protein/7.4.475. [DOI] [PubMed] [Google Scholar]
  12. Murzin A. G. Structural classification of proteins: new superfamilies. Curr Opin Struct Biol. 1996 Jun;6(3):386–394. doi: 10.1016/s0959-440x(96)80059-5. [DOI] [PubMed] [Google Scholar]
  13. Thoden J. B., Holden H. M., Wesenberg G., Raushel F. M., Rayment I. Structure of carbamoyl phosphate synthetase: a journey of 96 A from substrate to product. Biochemistry. 1997 May 27;36(21):6305–6316. doi: 10.1021/bi970503q. [DOI] [PubMed] [Google Scholar]
  14. Waldrop G. L., Rayment I., Holden H. M. Three-dimensional structure of the biotin carboxylase subunit of acetyl-CoA carboxylase. Biochemistry. 1994 Aug 30;33(34):10249–10256. doi: 10.1021/bi00200a004. [DOI] [PubMed] [Google Scholar]
  15. Xu R. M., Carmel G., Sweet R. M., Kuret J., Cheng X. Crystal structure of casein kinase-1, a phosphate-directed protein kinase. EMBO J. 1995 Mar 1;14(5):1015–1023. doi: 10.1002/j.1460-2075.1995.tb07082.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Yamaguchi H., Kato H., Hata Y., Nishioka T., Kimura A., Oda J., Katsube Y. Three-dimensional structure of the glutathione synthetase from Escherichia coli B at 2.0 A resolution. J Mol Biol. 1993 Feb 20;229(4):1083–1100. doi: 10.1006/jmbi.1993.1106. [DOI] [PubMed] [Google Scholar]
  17. Zheng J., Knighton D. R., Xuong N. H., Taylor S. S., Sowadski J. M., Ten Eyck L. F. Crystal structures of the myristylated catalytic subunit of cAMP-dependent protein kinase reveal open and closed conformations. Protein Sci. 1993 Oct;2(10):1559–1573. doi: 10.1002/pro.5560021003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Zheng J., Knighton D. R., ten Eyck L. F., Karlsson R., Xuong N., Taylor S. S., Sowadski J. M. Crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MgATP and peptide inhibitor. Biochemistry. 1993 Mar 9;32(9):2154–2161. doi: 10.1021/bi00060a005. [DOI] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES