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. 2002 Oct;83(4):2202–2210. doi: 10.1016/S0006-3495(02)73980-5

Analysis of ice-binding sites in fish type II antifreeze protein by quantum mechanics.

Yuhua Cheng 1, Zuoyin Yang 1, Hongwei Tan 1, Ruozhuang Liu 1, Guangju Chen 1, Zongchao Jia 1
PMCID: PMC1302308  PMID: 12324437

Abstract

Many organisms living in cold environments can survive subzero temperatures by producing antifreeze proteins (AFPs) or antifreeze glycoproteins. In this paper we investigate the ice-binding surface of type II AFP by quantum mechanical methods, which, to the best of our knowledge, represents the first time that molecular orbital computational approaches have been applied to AFPs. Molecular mechanical approaches, including molecular docking, energy minimization, and molecular dynamics simulation, were used to obtain optimal systems for subsequent quantum mechanical analysis. We selected 17 surface patches covering the entire surface of the type II AFP and evaluated the interaction energy between each of these patches and two different ice planes using semi-empirical quantum mechanical methods. We have demonstrated the weak orbital overlay phenomenon and the change of bond orders in ice. These results consistently indicate that a surface patch containing 19 residues (K37, L38, Y20, E22, Y21, I19, L57, T56, F53, M127, T128, F129, R17, C7, N6, P5, G10, Q1, and W11) is the most favorable ice-binding site for both a regular ice plane and an ice plane where water O atoms are randomly positioned. Furthermore, for the first time the computation results provide new insights into the weakening of the ice lattice upon AFP binding, which may well be a primary factor leading to AFP-induced ice growth inhibition.

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Selected References

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

  1. Baardsnes J., Kondejewski L. H., Hodges R. S., Chao H., Kay C., Davies P. L. New ice-binding face for type I antifreeze protein. FEBS Lett. 1999 Dec 10;463(1-2):87–91. doi: 10.1016/s0014-5793(99)01588-4. [DOI] [PubMed] [Google Scholar]
  2. Bertrand J. A., Pignol D., Bernard J. P., Verdier J. M., Dagorn J. C., Fontecilla-Camps J. C. Crystal structure of human lithostathine, the pancreatic inhibitor of stone formation. EMBO J. 1996 Jun 3;15(11):2678–2684. [PMC free article] [PubMed] [Google Scholar]
  3. Chao H., Houston M. E., Jr, Hodges R. S., Kay C. M., Sykes B. D., Loewen M. C., Davies P. L., Sönnichsen F. D. A diminished role for hydrogen bonds in antifreeze protein binding to ice. Biochemistry. 1997 Dec 2;36(48):14652–14660. doi: 10.1021/bi970817d. [DOI] [PubMed] [Google Scholar]
  4. Chao H., Sönnichsen F. D., DeLuca C. I., Sykes B. D., Davies P. L. Structure-function relationship in the globular type III antifreeze protein: identification of a cluster of surface residues required for binding to ice. Protein Sci. 1994 Oct;3(10):1760–1769. doi: 10.1002/pro.5560031016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chen G., Jia Z. Ice-binding surface of fish type III antifreeze. Biophys J. 1999 Sep;77(3):1602–1608. doi: 10.1016/S0006-3495(99)77008-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Davies P. L., Sykes B. D. Antifreeze proteins. Curr Opin Struct Biol. 1997 Dec;7(6):828–834. doi: 10.1016/s0959-440x(97)80154-6. [DOI] [PubMed] [Google Scholar]
  7. DeLuca C. I., Chao H., Sönnichsen F. D., Sykes B. D., Davies P. L. Effect of type III antifreeze protein dilution and mutation on the growth inhibition of ice. Biophys J. 1996 Nov;71(5):2346–2355. doi: 10.1016/S0006-3495(96)79476-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deng G., Andrews D. W., Laursen R. A. Amino acid sequence of a new type of antifreeze protein, from the longhorn sculpin Myoxocephalus octodecimspinosis. FEBS Lett. 1997 Jan 27;402(1):17–20. doi: 10.1016/s0014-5793(96)01466-4. [DOI] [PubMed] [Google Scholar]
  9. Dinner A. R., Blackburn G. M., Karplus M. Uracil-DNA glycosylase acts by substrate autocatalysis. Nature. 2001 Oct 18;413(6857):752–755. doi: 10.1038/35099587. [DOI] [PubMed] [Google Scholar]
  10. Ewart K. V., Li Z., Yang D. S., Fletcher G. L., Hew C. L. The ice-binding site of Atlantic herring antifreeze protein corresponds to the carbohydrate-binding site of C-type lectins. Biochemistry. 1998 Mar 24;37(12):4080–4085. doi: 10.1021/bi972503w. [DOI] [PubMed] [Google Scholar]
  11. Ewart K. V., Rubinsky B., Fletcher G. L. Structural and functional similarity between fish antifreeze proteins and calcium-dependent lectins. Biochem Biophys Res Commun. 1992 May 29;185(1):335–340. doi: 10.1016/s0006-291x(05)90005-3. [DOI] [PubMed] [Google Scholar]
  12. Ewart K. V., Yang D. S., Ananthanarayanan V. S., Fletcher G. L., Hew C. L. Ca2+-dependent antifreeze proteins. Modulation of conformation and activity by divalent metal ions. J Biol Chem. 1996 Jul 12;271(28):16627–16632. doi: 10.1074/jbc.271.28.16627. [DOI] [PubMed] [Google Scholar]
  13. Feeney R. E., Burcham T. S., Yeh Y. Antifreeze glycoproteins from polar fish blood. Annu Rev Biophys Biophys Chem. 1986;15:59–78. doi: 10.1146/annurev.bb.15.060186.000423. [DOI] [PubMed] [Google Scholar]
  14. Graether S. P., DeLuca C. I., Baardsnes J., Hill G. A., Davies P. L., Jia Z. Quantitative and qualitative analysis of type III antifreeze protein structure and function. J Biol Chem. 1999 Apr 23;274(17):11842–11847. doi: 10.1074/jbc.274.17.11842. [DOI] [PubMed] [Google Scholar]
  15. Graether S. P., Kuiper M. J., Gagné S. M., Walker V. K., Jia Z., Sykes B. D., Davies P. L. Beta-helix structure and ice-binding properties of a hyperactive antifreeze protein from an insect. Nature. 2000 Jul 20;406(6793):325–328. doi: 10.1038/35018610. [DOI] [PubMed] [Google Scholar]
  16. Gronwald W., Loewen M. C., Lix B., Daugulis A. J., Sönnichsen F. D., Davies P. L., Sykes B. D. The solution structure of type II antifreeze protein reveals a new member of the lectin family. Biochemistry. 1998 Apr 7;37(14):4712–4721. doi: 10.1021/bi972788c. [DOI] [PubMed] [Google Scholar]
  17. Haymet A. D., Ward L. G., Harding M. M., Knight C. A. Valine substituted winter flounder 'antifreeze': preservation of ice growth hysteresis. FEBS Lett. 1998 Jul 3;430(3):301–306. doi: 10.1016/s0014-5793(98)00652-8. [DOI] [PubMed] [Google Scholar]
  18. Jia Z., DeLuca C. I., Chao H., Davies P. L. Structural basis for the binding of a globular antifreeze protein to ice. Nature. 1996 Nov 21;384(6606):285–288. doi: 10.1038/384285a0. [DOI] [PubMed] [Google Scholar]
  19. Jia Zongchao, Davies Peter L. Antifreeze proteins: an unusual receptor-ligand interaction. Trends Biochem Sci. 2002 Feb;27(2):101–106. doi: 10.1016/s0968-0004(01)02028-x. [DOI] [PubMed] [Google Scholar]
  20. Knight C. A., Cheng C. C., DeVries A. L. Adsorption of alpha-helical antifreeze peptides on specific ice crystal surface planes. Biophys J. 1991 Feb;59(2):409–418. doi: 10.1016/S0006-3495(91)82234-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lee C, Yang W, Parr RG. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B Condens Matter. 1988 Jan 15;37(2):785–789. doi: 10.1103/physrevb.37.785. [DOI] [PubMed] [Google Scholar]
  22. Liou Y. C., Tocilj A., Davies P. L., Jia Z. Mimicry of ice structure by surface hydroxyls and water of a beta-helix antifreeze protein. Nature. 2000 Jul 20;406(6793):322–324. doi: 10.1038/35018604. [DOI] [PubMed] [Google Scholar]
  23. Loewen M. C., Gronwald W., Sönnichsen F. D., Sykes B. D., Davies P. L. The ice-binding site of sea raven antifreeze protein is distinct from the carbohydrate-binding site of the homologous C-type lectin. Biochemistry. 1998 Dec 22;37(51):17745–17753. doi: 10.1021/bi9820513. [DOI] [PubMed] [Google Scholar]
  24. Madura J. D., Baran K., Wierzbicki A. Molecular recognition and binding of thermal hysteresis proteins to ice. J Mol Recognit. 2000 Mar-Apr;13(2):101–113. doi: 10.1002/(SICI)1099-1352(200003/04)13:2<101::AID-JMR493>3.0.CO;2-9. [DOI] [PubMed] [Google Scholar]
  25. Patard L., Stoven V., Gharib B., Bontems F., Lallemand J. Y., De Reggi M. What function for human lithostathine?: structural investigations by three-dimensional structure modeling and high-resolution NMR spectroscopy. Protein Eng. 1996 Nov;9(11):949–957. doi: 10.1093/protein/9.11.949. [DOI] [PubMed] [Google Scholar]
  26. Raymond J. A., DeVries A. L. Adsorption inhibition as a mechanism of freezing resistance in polar fishes. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2589–2593. doi: 10.1073/pnas.74.6.2589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sicheri F., Yang D. S. Ice-binding structure and mechanism of an antifreeze protein from winter flounder. Nature. 1995 Jun 1;375(6530):427–431. doi: 10.1038/375427a0. [DOI] [PubMed] [Google Scholar]
  28. Sönnichsen F. D., DeLuca C. I., Davies P. L., Sykes B. D. Refined solution structure of type III antifreeze protein: hydrophobic groups may be involved in the energetics of the protein-ice interaction. Structure. 1996 Nov 15;4(11):1325–1337. doi: 10.1016/s0969-2126(96)00140-2. [DOI] [PubMed] [Google Scholar]
  29. Sönnichsen F. D., Sykes B. D., Davies P. L. Comparative modeling of the three-dimensional structure of type II antifreeze protein. Protein Sci. 1995 Mar;4(3):460–471. doi: 10.1002/pro.5560040313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wierzbicki A., Madura J. D., Salmon C., Sönnichsen F. Modeling studies of binding of sea raven type II antifreeze protein to ice. J Chem Inf Comput Sci. 1997 Nov-Dec;37(6):1006–1010. doi: 10.1021/ci9702353. [DOI] [PubMed] [Google Scholar]
  31. Yang D. S., Hon W. C., Bubanko S., Xue Y., Seetharaman J., Hew C. L., Sicheri F. Identification of the ice-binding surface on a type III antifreeze protein with a "flatness function" algorithm. Biophys J. 1998 May;74(5):2142–2151. doi: 10.1016/S0006-3495(98)77923-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yang D. S., Sax M., Chakrabartty A., Hew C. L. Crystal structure of an antifreeze polypeptide and its mechanistic implications. Nature. 1988 May 19;333(6170):232–237. doi: 10.1038/333232a0. [DOI] [PubMed] [Google Scholar]
  33. Yeh Yin, Feeney Robert E. Antifreeze Proteins: Structures and Mechanisms of Function. Chem Rev. 1996 Mar 28;96(2):601–618. doi: 10.1021/cr950260c. [DOI] [PubMed] [Google Scholar]

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