Biomaterial Database

Intramolecular general acid catalysis in the binding reactions of alpha 2-macroglobulin and complement components C3 and C4. 1981

S G Davies, and R B Sim

The complement system proteins C3 and C4 and the plasma protease inhibitor alpha 2-macroglobulin, when activated by limited proteolysis, can bind covalently to other macromolecules. The three proteins also exhibit an unusual internal peptide-bond cleavage reaction when denatured. The covalent binding reaction is likely to occur by a transacylation mechanism involving an internal thiolester in the three proteins. However, the activated species of these proteins are much more reactive than simple thiolesters. Studies of molecular models of the thiolester region in C3 show that an intramolecular acid catalysis mechanism can both account for the exceptional reactivity of the activated form of these proteins and provide an explanation for the denaturation-induced peptide bond cleavage.

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
D002384	Catalysis	The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.	Catalyses
D002621	Chemistry	A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D003176	Complement C3	A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.	C3 Complement,C3 Precursor,Complement 3,Complement C3 Precursor,Complement Component 3,Precursor-Complement 3,Pro-C3,Pro-Complement 3,C3 Precursor, Complement,C3, Complement,Complement, C3,Component 3, Complement,Precursor Complement 3,Precursor, C3,Precursor, Complement C3,Pro C3,Pro Complement 3
D003181	Complement C4	A glycoprotein that is important in the activation of CLASSICAL COMPLEMENT PATHWAY. C4 is cleaved by the activated COMPLEMENT C1S into COMPLEMENT C4A and COMPLEMENT C4B.	C4 Complement,C4 Complement Component,Complement 4,Complement C4, Precursor,Complement Component 4,Pro-C4,Pro-complement 4,C4, Complement,Complement Component, C4,Complement, C4,Component 4, Complement,Component, C4 Complement,Pro C4,Pro complement 4
D006860	Hydrogen Bonding	A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.	Hydrogen Bonds,Bond, Hydrogen,Hydrogen Bond
D000511	alpha-Macroglobulins	Glycoproteins with a molecular weight of approximately 620,000 to 680,000. Precipitation by electrophoresis is in the alpha region. They include alpha 1-macroglobulins and alpha 2-macroglobulins. These proteins exhibit trypsin-, chymotrypsin-, thrombin-, and plasmin-binding activity and function as hormonal transporters.	Slow alpha 2-Macroglobulins,alpha 2-Acute Phase Globulins,alpha-Macrofetoproteins,45S RNP,Acute-Phase alpha 1-Protein,Slow alpha 2-Globulin,alpha 1-Acute Phase Globulin,alpha 1-Acute Phase Protein,alpha 1-Macroglobulin,alpha 2-Acute Phase Globulin,alpha-Macrofetoprotein,Acute Phase alpha 1 Protein,RNP, 45S,Slow alpha 2 Globulin,Slow alpha 2 Macroglobulins,alpha 1 Acute Phase Globulin,alpha 1 Acute Phase Protein,alpha 1 Macroglobulin,alpha 1-Protein, Acute-Phase,alpha 2 Acute Phase Globulin,alpha 2 Acute Phase Globulins,alpha 2-Globulin, Slow,alpha 2-Macroglobulins, Slow,alpha Macrofetoprotein,alpha Macrofetoproteins,alpha Macroglobulins
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
D055598	Chemical Phenomena	The composition, structure, conformation, and properties of atoms and molecules, and their reaction and interaction processes.	Chemical Concepts,Chemical Processes,Physical Chemistry Concepts,Physical Chemistry Processes,Physicochemical Concepts,Physicochemical Phenomena,Physicochemical Processes,Chemical Phenomenon,Chemical Process,Physical Chemistry Phenomena,Physical Chemistry Process,Physicochemical Phenomenon,Physicochemical Process,Chemical Concept,Chemistry Process, Physical,Chemistry Processes, Physical,Concept, Chemical,Concept, Physical Chemistry,Concept, Physicochemical,Concepts, Chemical,Concepts, Physical Chemistry,Concepts, Physicochemical,Phenomena, Chemical,Phenomena, Physical Chemistry,Phenomena, Physicochemical,Phenomenon, Chemical,Phenomenon, Physicochemical,Physical Chemistry Concept,Physicochemical Concept,Process, Chemical,Process, Physical Chemistry,Process, Physicochemical,Processes, Chemical,Processes, Physical Chemistry,Processes, Physicochemical