|Gennadiy Moiseyev, PhD
Assistant Professor of Research
941 Stanton L. Young Blvd., BSEB 302C
Oklahoma City, OK 73104
(405) 271-5896 ext 48443
- Visual pigments of retina photoreceptors consist of 11-cis retinal chromophore covalently attached by Schiff base bonds to opsin proteins. The process of vision is initiated by photochemical reactions in photoreceptors resulting in isomerization of 11-cis retinal chromophores to all-trans retinal. The latter is then reduced to all-trans retinol and transported in retinal pigment epithelium (RPE). The photoisomerisation of retinal in the retina triggers the phototransduction cascade. Efficient recycling of the 11-cis retinal chromophore in rhodopsin is absolutely necessary to support normal vision.
This 11-cis retinal chromophore regeneration proceeds through the series of enzymatic reactions of retinoids in the RPE. We study the enzymes of the visual cycle, especially RPE65 protein which is crucial for reverse isomerization of all-trans retinyl ester to 11-cis retinol. Mutations in the RPE 65 gene results in severe retinal degenerations and early-onset blindness. The goal of the work is to establish the physiological role of RPE65 and the mechanism of its action.
||PhD - Chemistry, Institute of Molecular Biology, USSR Academy of Sciences, Moscow, USSR
||MS - Engineering & Physics, Moscow Physical Technical Institute, Moscow, USSR
Nikolaeva O, Takahashi Y, Moiseyev G*, and Ma JX. (2010). (*corresponding author). Negative charge of the glutamic acid 417 residue is crucial for isomerohydrolase activity of RPE65. Biochem. Biophys Res. Commun. Jan 22;391(4):1757-61.
Chen Y, Hu Y, Moiseyev G, Zhou KK, Chen D, and Ma JX. (2009). Photoreceptor degeneration and retinal inflammation induced by very low-density lipoprotein receptor deficiency. Microvasc Res. Jun;78(1):119-27.
Farjo KM, Moiseyev G, Takahashi Y, Crouch RK, and Ma JX. (2009). RDH10 has 11-cis-Retinol Dehydrogenase Activity and Interacts with Visual Cycle Proteins. Invest Ophthalmol Vis. Sci. Nov;50(11):5089-97.
Nikolaeva O, Takahashi Y, Moiseyev G*, and Ma JX. (2009). (*corresponding author). Purified RPE65 shows isomerohydrolase activity after reassociation with a phospholipid membrane. FEBS J. Jun;276(11):3020-30.
Takahashi Y, Moiseyev G, Farjo K, and Ma JX. (2009). Characterization of key residues and membrane association domains in RDH10. Biochem J. Apr 1;419(1):113-22
Takahashi Y, Moiseyev G, Ablonczy Z, Chen Y, Crouch RK, and Ma JX. (2008). Identification of a novel palmitilation site essential for membrane association and isomerohydrolase activity RPE65. J Biol Chem. Mar 28;283(13):8110-7.
Moiseyev G, Takahashi Y, Chen Y, Kim S, and Ma JX. (2008). RPE65 from cone-dominant chicken is a more efficient isomerohydrolase, compared to that from rod-dominant species. J Biol Chem. Mar 28;283(13):8110-7.
Kanan Y, Kasus-Jacobi A, Moiseyev G, Sawyer K, Ma JX, and Al-Ubaidi MR. (2008). Retinoid processing in cone and Müller cell lines. Exp Eye Res. Feb;86(2):344-54.
Sandell LL, Sanderson BW, Moiseyev G, Johnson T, Mushegian A, Young K, Rey JP, Ma JX, Staehling- Hampton K, and Trainor PA. (2007). RDH10 is essential for synthesis of embryonic retinoic acid and is required for limb, craniofacial, and organ development. Genes Dev. 21, 113-1124.
Kanan Y, Moiseyev G, Agarwal N, Ma JX, and Al-Ubaidi MR. (2007). Light induces programmed cell death by activating multiple independent proteases in a cone photoreceptor cell line. Invest Ophthalmol Vis Sci. Jan;48(1):40-51.
Chen Y, Moiseyev G, Takahashi Y, and Ma JX. (2006). Impacts of two point mutations of RPE65 from Leber's congenital amaurosis on the stability, subcellular localization and isomerohydrolase activity of RPE65. FEBS Lett. Jul 24;580(17):4200-4.
Takahashi Y, Chen Y, Moiseyev G, and Ma J-X. (2006). Two Point Mutations Of RPE65 From Patients With Retinal Dystrophies Decrease The Protein Stability and Abolish The Isomerohydrolase Activity Of RPE65. J. Biol. Chem. Aug 4;281(31):21820-6.
Moiseyev G, Takahashi Y, Chen Y, Gentleman S, Redmond TM, Crouch RK, and Ma J-X. (2006). RPE65 is an Iron(II)-dependent Isomerohydrolase in the Retinoid Visual Cycle. J. Biol. Chem 281, 2835-3840.
Chen Y, Moiseyev G, Takahashi Y, and Ma J-X. (2006). RPE65 gene delivery restores isomerohydrolase activity and prevents early cone loss in Rpe65-/- mice. Invest. Ophthalmol. Vis. Sci. 47:1177-84.
Takahashi Y, Moiseyev G, Chen Y, and Ma JX. (2006). The roles of three palmitoylation sites of RPE65 in its membrane association and isomerohydrolase activity, Invest Ophthalmol Vis Sci, 47(12):5191-6.
Takahashi Y, Moiseyev G, Chen Y, and Ma J.X. (2005). Identification of conserved histidines and glutamic acid as key residues for isomerohydrolase activity of RPE65, an enzyme of the visual cycle in the retinal pigment epithelium. FEBS Lett. 579:5414-5418.
Moiseyev G, Chen Y, Takahashi Y, Wu BX, and Ma J. (2005). RPE65 Is The Isomerohydrolase In The Retinois Visual Cycle. Proc. Natl. Acad. Sci. USA 102:12413- 8.