title: A point mutation converts dihydroneopterin aldolase to a cofactor-independent oxygenase.
abstract: Dihydroneopterin aldolase (DHNA) catalyzes the conversion of 7,8-dihydroneopterin (1) to 6-hydroxymethyl-7,8-dihydropterin (4) in the folate biosynthetic pathway. Substitution of a conserved tyrosine residue at the active site of DHNA by phenylalanine converts the enzyme to a cofactor-independent oxygenase, which generates mainly 7,8-dihydroxanthopterin (6) rather than 4. 6 is generated via the same enol intermediate as in the wild-type enzyme-catalyzed reaction, but this species undergoes an oxygenation reaction to form 6. The conserved tyrosine residue plays only a minor role in the formation of the enol reaction intermediate but a critical role in the protonation of the enol intermediate to form 4.
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, 48824, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Gwynyth
authors.initials: G
authors.lastname: Scherperel
authors.forename: Kade D
authors.initials: KD
authors.lastname: Roberts
authors.forename: A Daniel
authors.initials: AD
authors.lastname: Jones
authors.forename: Gavin E
authors.initials: GE
authors.lastname: Reid
authors.forename: Honggao
authors.initials: H
authors.lastname: Yan
mesh_terms: D000446:Aldehyde-Lyases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D007700:Kinetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D010105:Oxygenases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017354:Point Mutation; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D010105:Oxygenases; D000446:Aldehyde-Lyases; C020044:dihydroneopterin aldolase; D010100:Oxygen