Biochemical defects in retina-specific human ATP binding cassette transporter nucleotide binding domain 1 mutants associated with macular degeneration.

The Journal of Biological Chemistry
Tatiana SuárezE E Biswas

Abstract

The retina-specific human ABC transporter (ABCR) functions in the retinal transport system and has been implicated in several inherited visual diseases, including Stargardt disease, fundus flavimaculatus, cone-rod dystrophy, and age-related macular degeneration. We have previously described a general ribonucleotidase activity of the first nucleotide binding domain (NBD1) of human ABCR (Biswas, E. E. (2001) Biochemistry 40, 8181-8187). In this communication, we present a quantitative study analyzing the effects of certain disease-associated mutations, Gly-863 --> Ala, Pro-940 --> Arg, and Arg-943 --> Gln on the nucleotide binding, and general ribonucleotidase activities of this domain. NBD1 proteins, harboring these mutations, were created through in vitro site-specific mutagenesis and expressed in Escherichia coli. Results of the enzyme-kinetic studies indicated that these mutations altered the ATPase and CTPase activities of NBD1. The G863A and P940R mutations were found to have significant attenuation of the rates of nucleotide hydrolysis and binding affinities. On the other hand, the R943Q mutation had small, but detectable reduction in its nucleotidase activity and nucleotide binding affinity. We have measured the nucleotid...Continue Reading

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Citations

Feb 8, 2005·Journal of Molecular Evolution·Alexander N YatsenkoJames R Lupski
Dec 23, 2004·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·B Jeroen KleveringCarel B Hoyng
Mar 4, 2014·Protein Expression and Purification·Yaroslav Tsybovsky, Krzysztof Palczewski
Apr 21, 2010·The Journal of Biological Chemistry·Esther E Biswas-FissSubhasis B Biswas
Mar 28, 2012·Ophthalmology·Sarah C Westeneng-van HaaftenCarel B Hoyng
Oct 21, 2004·European Journal of Human Genetics : EJHG·B Jeroen KleveringFrans P M Cremers
May 20, 2003·Human Mutation·Alexander N YatsenkoJames R Lupski
Sep 5, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Jun WangRui Chen
Aug 31, 2021·Ophthalmic Genetics·Di HuangFred K Chen

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