IN SILICO ANALYSIS OF INTERACTIONS IN HEME BINDING PROTEINS
Keywords:Heme proteins, Iron-porphyrin complex, Non-covalent interactions, Stabilizing residues, Solvent accessibility, Ion-pairs
Objective: Heme cofactors are essential molecule found in almost all forms of life. Biological systems depend on heme-protein interactions to carry out basic functions required for their survival. The objective of the present work is to analyse the various non-covalent interactions and also focus on amino acid preferences in heme binding environment.
Methods: Various interactions like hydrophobic, aromatic and hydrogen bonds between heme and binding site of non-redundant dataset of 33 heme proteins were analysed to understand the characteristics of different type of interactions. Also the relative preference of amino acids participating in forming secondary structure, solvent accessibility, stabilizing residues and ion-pairs in heme binding environment was analysed.
Results: The analysis of heme binding protein environment revealed some important findings, which include the dominant role of non-polar contacts. 12% of the predicted stabilizing residues were also involved in forming interaction with heme. The secondary structure preference analysis showed that 41% of interacting residues preferred to be in helix. The frequency of non-polar amino acids in the buried region was predominant. The preference of amino acid Arg to form complete ion-pair was higher and these ion-pairs formed strong interactions. This provides insights into the better understanding of the heme environment.
Conclusion: The present findings through in silico analysis provide valuable information on natural heme binding proteins. These studies will contribute useful information regarding structural stability and its interaction in future designs of novel heme proteins.
Bikiel DE, Boechi L, Capece L, Crespo A. Modeling heme proteins using atomistic simulations. Phys Chem Chem Phys 2006;8:5611â€“28.
Paoli M, Marles-Wright J, Smith A. Structure-function relationships in heme-proteins. DNA Cell Biol 2002;21(4):271-80.
Reedy CJ, Gibney BR. Heme protein assemblies. Chem Rev 2004;104:617-49.
Sun J, Hoshino H, Takaku K. Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene. EMBO J 2002;21(19):5216-24.
Zenke-Kawasaki Y, Dohi Y, Katoh Y. Heme induces ubiquitination and degradation of the transcription factor Bach1. Mol Cell Biol 2007;27(19):6962-71.
Tang XD, Xu R, Reynolds MF. Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK channels. Nature 2003;425(6957):531-5.
Kaasik K, Lee CC. Reciprocal regulation of haem biosynthesis and the circadian clock in mammals. Nature 2004;430(6998):467-71.
Faller M, Matsunaga M, Yin S. Heme is involved in micro RNA processing. Nat Struct Mol Biol 2007;14(1):23-9.
Li T, Bonkovsky HL, Guo J-T. Structural analysis of heme proteins: implications for design and prediction. BMC Struct Biol 2011;11:1-13.
Morokuma K, Musaev DG, editors. Computational modeling for homogeneous and enzymatic catalysis: a knowledge-base for designing efficient catalysis. Hoboken (NJ): John Wiley and Sons; 2008.
Berman HM, Westbrook J, Feng Z. The protein data bank. Nucl Acids Res 2000;28:235-42.
Sobolev V, Sorokine A, Prilusky J. Automated analysis of interatomic contacts in proteins. Bioinf 1999;15:327-32.
Geourjon C, Deleage G. SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments. Comput Appl Biosci 1995;11:681-4.
Fraczkiewicz R, Braun W. Exact and efficient analytical calculation of the accessible surface areas and their gradients for macromolecules. J Comput Chem 1998;19(3):319-33.
Magyar C, Gromiha MM, Pujadas G. SRide: a server for identifying stabilizing residues in proteins. Nucleic Acids Res 2005;33:303-5.
Shankar BAG, Sarani R, Michael D. Ion pairs in non-redundant protein structures. J Biosci 2007;32:693â€“704.
Balamurugan B, Roshan MNA Md, Hameed BS. PSAP: protein structure analysis package. J Appl Cryst 2007;40:773-7.
Tina KG, Bhadra R, Srinivasan N. PIC: protein interactions calculator. Nucl Acids Res 2007;35:W473â€“W6.