Biomaterial Database

Stereochemical evidence for the evolution of pyridoxal-phosphate enzymes of various function from a common ancestor. 1974

H C Dunathan, and J G Voet

Several pyridoxal-phosphate-dependent enzymes can convert the bound cofactor to pyridoxamine phosphate. This conversion may be an obligatory part of the normal catalytic sequence, as with transaminases, or may be an abnormal path, inactivating the enzyme. This conversion requires protonation of the C(4)' carbon of the cofactor, which has now been shown to proceed stereospecifically and with the same absolute stereochemistry in seven quite different pyridoxal-phosphate enzymes. We report on one of these, tryptophan synthase B protein. This regularity in protonation stereochemistry suggests a remarkable regularity in the geometry of cofactor binding to the apoenzyme. This regularity is interpreted as evidence for the evolution of this entire family of enzymes from a common progenitor which, through the course of evolution, could not invert its original, arbitrary binding stereochemistry without passing through catalytically inactive conformations.

UI	MeSH Term	Description	Entries
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
D011522	Protons	Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion.	Hydrogen Ions,Hydrogen Ion,Ion, Hydrogen,Ions, Hydrogen,Proton
D011732	Pyridoxal Phosphate	This is the active form of VITAMIN B 6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (PYRIDOXAMINE).	Pyridoxal 5-Phosphate,Pyridoxal-P,Phosphate, Pyridoxal,Pyridoxal 5 Phosphate,Pyridoxal P
D002384	Catalysis	The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.	Catalyses
D005075	Biological Evolution	The process of cumulative change over successive generations through which organisms acquire their distinguishing morphological and physiological characteristics.	Evolution, Biological
D000637	Transaminases	A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. (Dorland, 28th ed) EC 2.6.1.	Aminotransferase,Aminotransferases,Transaminase
D013237	Stereoisomerism	The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014367	Tryptophan Synthase	An enzyme that catalyzes the conversion of L-serine and 1-(indol-3-yl)glycerol 3-phosphate to L-tryptophan and glyceraldehyde 3-phosphate. It is a pyridoxal phosphate protein that also catalyzes the conversion of serine and indole into tryptophan and water and of indoleglycerol phosphate into indole and glyceraldehyde phosphate. (From Enzyme Nomenclature, 1992) EC 4.2.1.20.	Tryptophan Synthetase,Synthase, Tryptophan,Synthetase, Tryptophan