5tce
From Proteopedia
N-terminal microdomain of 34-mers from HsDHODH - N-t(DH)
Structural highlights
Disease[PYRD_HUMAN] Defects in DHODH are the cause of postaxial acrofacial dysostosis (POADS) [MIM:263750]; also known as Miller syndrome. POADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases.[1] Function[PYRD_HUMAN] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor. Publication Abstract from PubMedThe 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. Conformational changes of the HsDHODH N-terminal Microdomain via DEER Spectroscopy.,Vicente EF, Sahu ID, Costa-Filho AJ, Cilli EM, Lorigan GA J Phys Chem B. 2015 Jul 16;119(28):8693-7. doi: 10.1021/acs.jpcb.5b01706. Epub, 2015 Jul 2. PMID:26086954[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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