Biomaterial Database

Binding specificity of papain and cathepsin B. 1986

K Akahane, and H Umeyama

In order to obtain useful information for the design of inhibitors of cathepsin B, an important enzyme in both physiological and pathological processes, the modes of interaction between ligands and thiol proteases (papain and cathepsin B) were analyzed. A new and powerful method was developed to quantitatively understand geometrical features of the interaction. Fairly good electrostatic complementarities were found for the oxygen atoms of P1 and P2 amide, and for the hydrogen atom of P2 amide. Electrostatic correlation potentials on the side chains of P1 and P2 were nearly neutral, so that interacting conformations in these regions are anticipated to be stabilized by hydrophobic forces rather than electrostatic ones. A three-dimensional structure of rat liver cathepsin B was deduced based on the assumption that the tertiary structure of cathepsin B is similar to that of actinidin. Furthermore, an inhibitor of the thiol proteases, benzyloxycarbonyl-L-phenylalanyl-L-alanine chloromethyl ketone was model fitted to cathepsin B, in order to investigate its mode of interaction with the enzyme. It was possible to account for some structure-activity relationships in the enzyme-ligand interactions.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D010206	Papain	A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and CHYMOPAPAIN that is used as a topical enzymatic debriding agent. EC 3.4.22.2.	Tromasin
D010450	Endopeptidases	A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.	Endopeptidase,Peptide Peptidohydrolases
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
D002401	Cathepsin B	A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.	Cathepsin B-Like Proteinase,Cathepsin B1,Cathepsin B Like Proteinase,Proteinase, Cathepsin B-Like
D003196	Computer Graphics	The process of pictorial communication, between human and computers, in which the computer input and output have the form of charts, drawings, or other appropriate pictorial representation.	Computer Graphic,Graphic, Computer,Graphics, Computer
D003546	Cysteine Endopeptidases	ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
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