Biomaterial Database

Effect of Single-Point Mutations on Nitric Oxide Rebinding and the Thermodynamic Stability of Myoglobin. 2019

Polydefkis Diamantis, and Krystel El Hage, and Markus Meuwly

Department of Chemistry , University of Basel , Klingelbergstrasse 80 , 4056 Basel , Switzerland.

The effect of single amino acid mutations on the rebinding dynamics of nitrogen monoxide (NO) to myoglobin is investigated using reactive molecular dynamics simulations. In particular, mutations of residues surrounding the heme-active site (Leu29, His64, Val68) were considered. Consistent with experiments, all mutations studied here have a significant effect on the kinetics of the NO-rebinding process, which consists of a rapid (several 10 ps) and a slow (100s of ps) time scale. For all modifications considered, the time scales and rebinding fractions agree to within a few percents with results from experiments by adjusting one single, physically meaningful, conformationally averaged quantity: the asymptotic energy separation between the NO-bound (2A) and photodissociated (4A) states. It is furthermore shown that the thermodynamic stability of wild-type versus mutant Mb for the ligand-free and ligand-bound variants of the protein can be described by the same computational model. Therefore, ligand kinetics and thermodynamics are related in a direct fashion akin to Φ-value analysis, which establishes a relationship between protein folding rates and thermal stability of proteins.

UI	MeSH Term	Description	Entries
D009211	Myoglobin	A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group.
D009569	Nitric Oxide	A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.	Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D006418	Heme	The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.	Ferroprotoporphyrin,Protoheme,Haem,Heme b,Protoheme IX
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013816	Thermodynamics	A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)	Thermodynamic
D017354	Point Mutation	A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.	Mutation, Point,Mutations, Point,Point Mutations
D055550	Protein Stability	The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.	Protein Stabilities,Stabilities, Protein,Stability, Protein
D056004	Molecular Dynamics Simulation	A computer simulation developed to study the motion of molecules over a period of time.	Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics