title: Conformational changes of the HsDHODH N-terminal Microdomain via DEER Spectroscopy.
abstract: The human enzyme dihydroorotate dehydrogenase (HsDHODH) has been studied for being a target for development of new antineoplasic and antiproliferative drugs. The synthetic peptide N-t(DH) represents the N-terminal microdomain of this enzyme, responsible for anchoring it to the inner mitochondrial membrane. Also, it is known to harbor quinones that are essential for enzyme catalysis. Here we report structural features of the peptide/membrane interactions obtained by using CD and DEER spectroscopic techniques, both in micelles and in lipid vesicles. The data revealed different peptide conformational states in micelles and liposomes, which could suggest that this microdomain acts in specific regions or areas of the mitochondria, which can be related with the control of the quinone access to the HsDHODH active site. This is the first study to report on conformational changes of the HsDHODH N-terminal microdomain through a combination of CD and DEER spectroscopic techniques.
authors.affiliation: †UNESP - Univ Estadual Paulista, Campus de Tupã, 17602-496, Tupã, SP Brazil.
authors.forename: Eduardo F
authors.initials: EF
authors.lastname: Vicente
authors.affiliation: ‡Department of Chemistry and Biochemistry, Miami University, 45056, Oxford, Ohio United States.
authors.forename: Indra D
authors.initials: ID
authors.lastname: Sahu
authors.affiliation: §Laboratório de Biofísica Molecular, Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo - USP,14040-901, Ribeirão Preto, SP Brazil.
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Costa-Filho
authors.affiliation: ∥Departamento de Bioquímica e Tecnologia Química, Instituto de Química, UNESP - Univ Estadual Paulista, 14800-900, Araraquara, SP Brazil.
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Cilli
authors.affiliation: ‡Department of Chemistry and Biochemistry, Miami University, 45056, Oxford, Ohio United States.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Lorigan
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D002942:Circular Dichroism; D000090722:Dihydroorotate Dehydrogenase; D006801:Humans; D008969:Molecular Sequence Data; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000737:chemistry*; D011487:Protein Conformation; D013057:Spectrum Analysis / Q000379:methods*
chemical_list: D000090722:Dihydroorotate Dehydrogenase; D044925:Oxidoreductases Acting on CH-CH Group Donors