Role of Disulfide Bonds in Stabilizing the Conformation of Selected Enzymes - An Approach Based on Divergence Entropy Applied to the Structure of Hydrophobic Core in Proteins

One of the factors responsible for tertiary structural stabilization in proteins is the presence of the hydrophobic core—a result of hydrophobic interactions within the protein body. In some proteins (especially extracellular ones) additional stabilization is provided by covalent bonds between selected Cys residues, commonly referred to as disulfide bonds. The mutual interplay of both factors and their respective contributions to stabilization are the focus of this work. The assessment of the effects of disulfide bonds isinterpreted by Fuzzy Oil Drop (FOD) model in which individual polypeptide chain fragments (including fragments which participate in SS bonds) can be evaluated in the context of their influence upon tertiary structural stabilization by comparing their corresponding theoretical and idealized hydrophobicity density distributions. The proteins were identified with both factors reinforcing each other, as well as proteins where they seem to counteract each other. The analysis presents a number of enzymes, including ribonuclease, lysozyme, disulfide isomerase and phospholipase.

[1]  M. Levitt.  A simplified representation of protein conformations for rapid simulation of protein folding. , 1976, Journal of molecular biology.

[2]  Y. Yamagata,et al.  A general rule for the relationship between hydrophobic effect and conformational stability of a protein: stability and structure of a series of hydrophobic mutants of human lysozyme. , 1998, Journal of molecular biology.

[3]  P J Artymiuk,et al.  Refinement of human lysozyme at 1.5 A resolution analysis of non-bonded and hydrogen-bond interactions. , 1981, Journal of molecular biology.

[4]  Arieh Ben-Naim.  Theoretical aspects of pressure and solute denaturation of proteins: A Kirkwood-buff-theory approach. , 2012, The Journal of chemical physics.

[5]  R. A. Leibler,et al.  On Information and Sufficiency , 1951 .

[6]  S Marangoni,et al.  Structural basis for low catalytic activity in Lys49 phospholipases A2--a hypothesis: the crystal structure of piratoxin II complexed to fatty acid. , 2001, Biochemistry.

[7]  Luis Moroder,et al.  The two cysteine-rich head domains of minicollagen from Hydra nematocysts differ in their cystine framework and overall fold despite an identical cysteine sequence pattern. , 2005, Journal of molecular biology.

[8]  Arieh Ben-Naim.  Theoretical aspects of self-assembly of proteins: a Kirkwood-Buff-theory approach. , 2013, The Journal of chemical physics.

[9]  Arieh Ben-Naim.  On the So-Called Gibbs Paradox, and on the Real Paradox , 2007, Entropy.

[10]  M. Sternberg,et al.  Analysis and classification of disulphide connectivity in proteins. The entropic effect of cross-linkage. , 1994, Journal of molecular biology.

[11]  Irena Roterman-Konieczna,et al.  Gauss-Function-Based Model of Hydrophobicity Density in Proteins , 2006, Silico Biol..

[12]  F. Schmid,et al.  A stable disulfide-free gene-3-protein of phage fd generated by in vitro evolution. , 2005, Journal of molecular biology.

[13]  Christopher M. Dobson,et al.  Structural basis of the stability of a lysozyme molten globule , 1995, Nature Structural Biology.

[14]  Arieh Ben-Naim,et al.  Myths and verities in protein folding theories: from Frank and Evans iceberg-conjecture to explanation of the hydrophobic effect. , 2013, The Journal of chemical physics.

[15]  Jonathan S. Weissman,et al.  A kinetic explanation for the rearrangement pathway of BPTI folding , 1995, Nature Structural Biology.

[16]  David S. Moss,et al.  Comparison of Two Independently Refined Models of Ribonuclease-A , 1986 .

[17]  W. Kauzmann.  Some factors in the interpretation of protein denaturation. , 1959, Advances in protein chemistry.

[18]  Ruhong Zhou,et al.  Interplay between drying and stability of a TIM barrel protein: a combined simulation-experimental study. , 2013, Journal of the American Chemical Society.

[19]  Kun Huang,et al.  Structure-specific effects of protein topology on cross-beta assembly: studies of insulin fibrillation. , 2006, Biochemistry.

[20]  Mateusz Banach,et al.  Simulation of the Protein Folding Process , 2014 .

[21]  Jonathan S. Weissman,et al.  Efficient catalysis of disulphide bond rearrangements by protein disulphide isomerase , 1993, Nature.

[22]  J F Riordan,et al.  Crystal structure of human angiogenin reveals the structural basis for its functional divergence from ribonuclease. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Michel De Waard,et al.  The impact of the fourth disulfide bridge in scorpion toxins of the α‐KTx6 subfamily , 2005, Proteins.

[24]  Mateusz Banach,et al.  The fuzzy oil drop model, based on hydrophobicity density distribution, generalizes the influence of water environment on protein structure and function. , 2014, Journal of theoretical biology.

[25]  Irena Roterman-Konieczna,et al.  Catalytic residues in hydrolases: analysis of methods designed for ligand-binding site prediction , 2010, J. Comput. Aided Mol. Des..

[26]  Hermann Schindelin,et al.  The Catalytic Activity of Protein-disulfide Isomerase Requires a Conformationally Flexible Molecule* , 2008, Journal of Biological Chemistry.

[27]  Gur Pines,et al.  The ERBB network: at last, cancer therapy meets systems biology , 2012, Nature Reviews Cancer.

[28]  Lei Wang,et al.  Title : Plasticity of Human Protein Disulfide Isomerase : Evidence for Mobility Around the X-Linker Region and its Functional Significance Year of publication : 2010 , 2010 .

[29]  Mateusz Banach,et al.  Intrinsically disordered proteins--relation to general model expressing the active role of the water environment. , 2014, Advances in protein chemistry and structural biology.

[30]  Raghavan Varadarajan,et al.  Conformational analysis and design of cross‐strand disulfides in antiparallel β‐sheets , 2011, Proteins.

[31]  Hyun-soo Cho,et al.  Structure of the Extracellular Region of HER3 Reveals an Interdomain Tether , 2002, Science.

[32]  Christopher M. Dobson,et al.  Local Cooperativity in an Amyloidogenic State of Human Lysozyme Observed at Atomic Resolution , 2010, Journal of the American Chemical Society.

[33]  C. Dobson,et al.  The folding of hen lysozyme involves partially structured intermediates and multiple pathways , 1992, Nature.

[34]  Oxana V. Galzitskaya,et al.  Folding nuclei in proteins , 2001 .

[35]  J. Schrag,et al.  1.8 A refined structure of the lipase from Geotrichum candidum. , 1993, Journal of molecular biology.

[36]  Irena Roterman-Konieczna,et al.  Application of Divergence Entropy to Characterize the Structure of the Hydrophobic Core in DNA Interacting Proteins , 2015, Entropy.

[37]  M Nilges,et al.  Structure determination of the N-terminal thioredoxin-like domain of protein disulfide isomerase using multidimensional heteronuclear 13C/15N NMR spectroscopy. , 1996, Biochemistry.

[38]  Donald J. Jacobs,et al.  Changes in Lysozyme Flexibility upon Mutation Are Frequent, Large and Long-Ranged , 2012, PLoS Comput. Biol..

[39]  C. Anfinsen.  Principles that govern the folding of protein chains. , 1973, Science.

[40]  T. Creighton.  Disulphide bonds and protein stability , 1988, BioEssays : news and reviews in molecular, cellular and developmental biology.