title: Kinemage of action - proposed reaction mechanism of glutamate-1-semialdehyde aminomutase at an atomic level.
abstract: Glutamate-1-semialdehyde aminomutase (GSAM), a key enzyme in tetrapyrrole cofactor biosynthesis, performs a unique transamination on a single substrate. The substrate, glutamate-1-semialdehyde (GSA), undergoes a reaction that exchanges the position of an amine and a carbonyl group to produce 5-aminolevulinic acid (ALA). This transamination reaction is unique in the fact that is does not require an external cofactor to act as a nitrogen donor or acceptor in this transamination reaction. One of the other remarkable features of the catalytic mechanism is the release free in the enzyme active site of the intermediate 4,5-diaminovaleric acid (DAVA). The action of a gating loop prevents the escape of DAVA from the active site. In a MD simulation approach, using snapshots provided by X-ray crystallography and protein crystal absorption spectrometry data, the individual catalytic steps in this unique intramolecular transamination have been elucidated.
authors.affiliation: Department of Chemistry, University of Manitoba, Winnipeg, Canada R3T 2N2. John_Sorensen@umanitoba.ca
authors.forename: John L
authors.initials: JL
authors.lastname: Sorensen
authors.forename: Jörg
authors.initials: J
authors.lastname: Stetefeld
mesh_terms: D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D005971:Glutamates / Q000737:chemistry*; D019751:Intramolecular Transferases / Q000737:chemistry*; D007700:Kinetics; D011487:Protein Conformation; D013379:Substrate Specificity; D025101:Vitamin B 6 / Q000737:chemistry
chemical_list: D005971:Glutamates; C057794:glutamate-1-semialdehyde; D025101:Vitamin B 6; D019751:Intramolecular Transferases; C061049:glutamate-1-semialdehyde 2,1-aminomutase