Literature summary for 3.4.21.76 extracted from

Hajjar, E.; Dejaegere, A.; Reuter, N.
Challenges in pKa predictions for proteins: the case of Asp213 in human proteinase 3 (2009), J. Phys. Chem. A, 113, 11783-11792.

Search for more literature for 3.4.21.76

Application

Application	Comment	Organism
analysis	knowledge of the protonation states of the ionizable residues in an enzyme like PR3 is a prerequisite to an accurate description of its structure and mechanism	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
Val-Ala-Asp-Val-Lys-Asp-Arg + H2O	simulations with a neutral Asp213 bound to the peptide reproduce the expected conformation of the catalytic triad: there are strong hydrogen bonds between histidine 57 and serine 195 and between histidine 57 and the aspartic acid 102. When Asp213 is ionized and in the presence of a peptide bound in the enzyme, its side chain moves away from Gly197 and toward Ser195. The resulting interaction between Asp213 and Ser195 is strong with the formation of a hydrogen bond that persists for over 90% of the simulation time. Interaction competes with the crucial Ser-His hydrogen of the catalytic triad altering the proteolytic function of the enzyme. The pKa for Asp213 is of 8.4 (with a fast empirical method or based on molecular dynamics simulations). In simulations with negatively charged form of Asp213 the interaction between the carbonyl of the P1 residue (oxyanion hole) of the substrate and Ser195 (NH) of PR3 has vanished and the favorable interactions between the enzyme and the substrate are disrupted. A strong hydrogen bond is formed between the imidazole ring of His57 and the P1 and P1' residues of the substrate (NH groups) lasting 83 and 55% of the simulation time, respectively. These hydrogen bonds compete with, or replace, the crucial ones between amino acids of the catalytic triad and in particular the Ser-His interaction	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
PR3	-	Homo sapiens
proteinase 3	-	Homo sapiens

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Release 2023.1 (January 2023)