<b>Steric Course and Specificity of α-Chymotrypsin-catalyzed Reactions. I</b>

Hein, George E.; Niemann, Carl

doi:10.1021/ja00882a024

Cited by 105 publications

(47 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…57.5-58 "C, [aIDZ2 + 30.1' (c, 5 in sym-tetrachloroethane). This agrees well with previously reported results (16,19).…”

Section: Methodssupporting

confidence: 94%

pH Effects in trypsin catalysis

Kasserra¹,

Laidler²

1969

Can. J. Chem.

View full text Add to dashboard Cite

A kinetic study has been made of the trypsin-catalyzed hydrolysis of N-benzoyl-L-alanine methyl ester, at p H values ranging from 6 to 10. The substrate concentrati~ns varied from 1.7 x to 4.3 x M. From the rates were calculated, at each pH, values of kc (corresponding to [S] >> K,,,), k,/f?,,,, (corresponding to [S] << K,,,) and K,,,. The specific levorotation of trypsin was measured and found to vary with p H in the p H region 5-1 1, the change in specific rotation following the ionization of a single group with pK(app) of 9.4. At p H 11 the specific rotation of trypsin, its zymogen, and its phosphorylated derivative were approximately the same, suggesting similar conformations for all three forms of the protein.The kinetic results on the acid side were very similar to those obtained by other investigators for chymotrypsin; they imply that there is a group of pK, z 7 in the free enzyme, presumably the imidazole function of a histidine residue, and that this group is involved in acylation and deacylation, which can only occur if it is unprotonated. The behavior on the basic side was found to be different from that with chymotrypsin revealing a decrease in kc at high p H corresponding to a value of pK, z 9.5, whereas kc/I?,,, showed sigmoid pH-dependence. A n interpretation of these results that is consistent with all available information is that a group of pK z 9.5 (presumably the -NH3+ function of the terminal isoleucine) controls the conformation and thereby the activity of the enzyme at different stages of complex formation. In contrast to chymotrypsin, the pK of this ionizing group appears to be generally lowered by covalent complex formation between trypsin and its substrates.

show abstract

“…57.5-58 "C, [aIDZ2 + 30.1' (c, 5 in sym-tetrachloroethane). This agrees well with previously reported results (16,19).…”

Section: Methodssupporting

confidence: 94%

pH Effects in trypsin catalysis

Kasserra¹,

Laidler²

1969

Can. J. Chem.

View full text Add to dashboard Cite

show abstract

“…The D-isomer of this conformationally restricted ester is hydrolyzed at a rate comparable to that of N-acetylated L-phenylalanine methyl esters while the L-isomer is hydrolyzed very slowly. Hein and Niemann (101,102) …”

Section: Absolute Conformation Of Bound Substratementioning

confidence: 99%

Bioorganic Chemistry

Dugas

Penney

1981

Springer Advanced Texts in Chemistry

110

View full text Add to dashboard Cite

“…A small Km indicates high affinity, and a substrate with a smaller Km will approach Vmax more quickly. Very high C ( t ) values are required to approach Vmax , which is reached only when C ( t ) is high enough to saturate the enzyme (Hein and Niemann, 1962). …”

Section: Michaelis-menten Kinetic Equation and Two Compartmental Pmentioning

confidence: 99%

Statistical identifiability and convergence evaluation for nonlinear pharmacokinetic models with particle swarm optimization

Kim

2014

Computer Methods and Programs in Biomedicine

View full text Add to dashboard Cite

The statistical identifiability of nonlinear pharmacokinetic (PK) models with the Michaelis-Menten (MM) kinetic equation is considered using a global optimization approach, which is particle swarm optimization (PSO). If a model is statistically non-identifiable, the conventional derivative-based estimation approach is often terminated earlier without converging, due to the singularity. To circumvent this difficulty, we develop a derivative-free global optimization algorithm by combining PSO with a derivative-free local optimization algorithm to improve the rate of convergence of PSO. We further propose an efficient approach to not only checking the convergence of estimation but also detecting the identifiability of nonlinear PK models. PK simulation studies demonstrate that the convergence and identifiablity of the PK model can be detected efficiently through the proposed approach. The proposed approach is then applied to clinical PK data along with a two-compartmental model.

show abstract

Steric Course and Specificity of α-Chymotrypsin-catalyzed Reactions. I

Cited by 105 publications

References 3 publications

pH Effects in trypsin catalysis

pH Effects in trypsin catalysis

Bioorganic Chemistry

Statistical identifiability and convergence evaluation for nonlinear pharmacokinetic models with particle swarm optimization

Contact Info

Product

Resources

About