title: A novel mutation of the cytochrome-b5 reductase gene in an Indian patient: the molecular basis of type I methemoglobinemia.
abstract: We report here a novel mutation in the cytochrome b5 reductase gene resulting in type I methemoglobinemia. A single T->C transition in exon 8 at position 25985 was identified, changing codon 217 from Leu to Pro (L217P). The mutation is located in the NADH binding domain at the base of alpha-helix Nalpha3, a region of sequence highly conserved from yeast to man. A quantitative assessment of the thermodynamic cost of this mutation at 37 degrees C revealed a ten-fold drop in the free energy of stability. Alterations in hydrogen bonding and solvent accessibility surrounding residue 217 were predicted based on computer modeling.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas, 77030, USA.
authors.forename: Roberto H
authors.initials: RH
authors.lastname: Nussenzveig
authors.forename: H Bindu
authors.initials: HB
authors.lastname: Lingam
authors.forename: Amos
authors.initials: A
authors.lastname: Gaikwad
authors.forename: Qiqing
authors.initials: Q
authors.lastname: Zhu
authors.forename: Naijie
authors.initials: N
authors.lastname: Jing
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
mesh_terms: D000328:Adult; D042966:Cytochrome-B(5) Reductase / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008708:Methemoglobinemia / Q000201:enzymology* / Q000235:genetics*; D009154:Mutation; D013816:Thermodynamics
chemical_list: D042966:Cytochrome-B(5) Reductase