Probing hydration contributions to the thermodynamics of ligand binding by proteins. Enthalpy and heat capacity changes of tacrolimus and rapamycin binding to FK506 binding protein in deuterium oxide and water

Biochemistry ◽  
1993 ◽  
Vol 32 (21) ◽  
pp. 5583-5590 ◽  
Author(s):  
Patrick R. Connelly ◽  
John A. Thomson ◽  
Matthew J. Fitzgibbon ◽  
Frank J. Bruzzese
Keyword(s):  
Heat Capacity ◽  
Ligand Binding ◽  
Binding Protein ◽  
Deuterium Oxide ◽  
Fk506 Binding Protein ◽  
Heat Capacity Changes

Stabilization of the FK506 binding protein by ligand binding

1991 ◽  
Vol 179 (2) ◽  
pp. 741-748 ◽  
Author(s):  
Dorothy Marquis-Omer ◽  
Gautam Sanyal ◽  
David B. Volkin ◽  
Alice I. Marcy ◽  
H.Karen Chan ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Protein ◽  
Fk506 Binding Protein

scholarly journals An improved reversibly dimerizing mutant of the FK506-binding protein FKBP

2016 ◽  
Author(s):  
Juan J. Barrero ◽  
Effrosyni Papanikou ◽  
Jason C. Casler ◽  
Kasey J. Day ◽  
Benjamin S. Glick
Keyword(s):  
Ligand Binding ◽  
Secretory Pathway ◽  
Binding Protein ◽  
Binding Pocket ◽  
Ligand Binding Pocket ◽  
Fk506 Binding Protein ◽  
Ligand Addition

FK506-binding protein (FKBP) is a monomer that binds to FK506, rapamycin, and related ligands. The F36M substitution, in which Phe36 in the ligand-binding pocket is changed to Met, leads to formation of antiparallel FKBP dimers, which can be dissociated into monomers by ligand binding. This FKBP(M) mutant has been employed in the mammalian secretory pathway to generate aggregates that can be dissolved by ligand addition to create cargo waves. However, when testing this approach in yeast, we found that dissolution of FKBP(M) aggregates was inefficient. An improved reversibly dimerizing FKBP formed aggregates that dissolved more readily. This FKBP(L,V) mutant carries the F36L mutation, which increases the affinity of ligand binding, and the I90V mutation, which accelerates ligand-induced dissociation of the dimers. The FKBP(L,V) mutant expands the utility of reversibly dimerizing FKBP.

scholarly journals Catalytic and ligand binding properties of the FK506 binding protein FKBP12: effects of the single amino acid substitution of Tyr82 to Leu

1994 ◽  
Vol 297 (2) ◽  
pp. 365-372 ◽  
Author(s):  
M J Bossard ◽  
D J Bergsma ◽  
M Brandt ◽  
G P Livi ◽  
W K Eng ◽  
...  
Keyword(s):  
Amino Acid ◽  
Ligand Binding ◽  
Binding Protein ◽  
Single Amino Acid ◽  
Intermediate Step ◽  
Wild Type ◽  
Structural Element ◽  
Binding Properties ◽  
Gene Encoding ◽  
Fk506 Binding Protein

The binding of FK506 and rapamycin to their cytosolic receptor FKBP12 is an intermediate step in the paths leading to their potent immunosuppressive properties. One of the amino acids defining the hydrophobic binding cleft for the macrocycles is Tyr82, which is thought to form a hydrogen bond with the amide oxygens of the common pipecolyl structural element within the two macrolides. To understand better the influence of this amino acid residue in catalytic activity (cis-trans peptidyl prolyl isomerization) and ligand binding properties, a Tyr82 to Leu site-specific modification of FKBP12 was prepared, purified and characterized. Kinetic experiments have demonstrated that the Tyr82 to Leu modification has a greater effect on catalytic properties than on ligand binding affinities, a result which indicates that these inhibitors may not be binding as true transition-state analogues. In an additional test for cellular function, expression of both wild-type and mutant human FKBP12 in a strain of Saccharomyces cerevisiae rendered resistant to rapamycin by deletion of the gene encoding a cytosolic rapamycin binding protein (RPB1), the yeast homologue of FKBP12, restored wild-type drug sensitivity.

Aqueous nonelectrolyte solutions. Part XVI. Formula of deuterium sulfide D-hydrate and its dissociation thermodynamic functions

2000 ◽  
Vol 78 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Colin W Clarke ◽  
David N Glew
Keyword(s):  
Heat Capacity ◽  
Thermodynamic Functions ◽  
Standard Enthalpy ◽  
Approximate Formula ◽  
Deuterium Oxide ◽  
Equilibrium Constants ◽  
Hydrate Dissociation ◽  
Quadruple Point ◽  
Dissociation Equilibrium ◽  
Heat Capacity Changes

A method has been devised to approximate both the hydrate formula number n and the standard thermodynamic functions for hydrate dissociation from the temperature change of the hydrate former fugacity along a univariant three-phase (hl1g) equilibrium line. Thermodynamic equations are derived, their validity discussed, and an iterative method for their solution is described. The univariant (hl1g) equilibrium dissociation of deuterium sulfide D-hydrate (D2S·nD2O phase h) into gaseous deuterium sulfide (g) and liquid deuterium oxide (l1) has been treated to give approximate formulae and dissociation constants at 58 temperatures from 2.798 to 30.666°C. Dissociation equilibrium constants Kp(h–> l1g) have been represented as a function of temperature by a four-parameter equation which yields both values and standard errors (i) for ΔHot(h–> l1g) and ΔCpot(h–> l1g) the standard enthalpy and heat capacity changes for D-hydrate dissociation and (ii) for n = r the approximate formula number of the D-hydrate at each experimental temperature. The formula D2S·6.115D2O with standard error 0.018D2O is found for deuterium sulfide D-hydrate at lower quadruple point Q(hs1l1g) 3.392°C; an approximate formula D2S·5.840D2O with SE 0.019D2O is found at upper quadruple point Q(hs1l2g) 30.770°C. Key words: clathrate D-hydrate of deuterium sulfide, deuterium sulfide D-hyfrate, formula of deuterium sulfide D-hydrate, thermodynamics of clathrate hydrate dissociation, dissociation equilibrium constant of deuterium sulfide D-hydrate, standard enthalpy, and heat capacity changes for dissociation of deuterium sulfide D-hydrate.

Autoantibodies to FK506 Binding Protein 12 (FKBP12) in Autoimmune Diseases

Autoimmunity ◽  
1999 ◽  
Vol 29 (3) ◽  
pp. 159-170 ◽  
Author(s):  
Nobuhiko Shinkura ◽  
Iwao Ikai ◽  
Akira Yamauchl ◽  
Tetsuro Hirose ◽  
Yasuhiro Kawap ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Binding Protein ◽  
Fk506 Binding Protein
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