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نیلوفر برومند

The RP10 type of retinitis pigmentosa is believed to result from mutations in inosine monophosphate 5´ dehydrogenase 1 (IMPDH1). IMPDH1 contributes to the de novo synthesis of guanine nucleotides by converting the inosine monophosphate (IMP) to xanthosine monophosphate (XMP) during reduction of NAD+. The mouse retinal IMPDH1, IMPDH1(546) and IMPDH1(603), are structurally distinct from IMPDH1(514) (canonical isoform) by bearing terminal extensions. The impact of these terminal segments on the enzyme function has not yet been investigated. In this report, we investigated the impact of the terminal amino acid extensions on cofactor tolerance of the retinal IMPDH1 isoforms relative to that of the canonical isoform. So, enzyme kinetic assay of the mouse IMPDH1 isoforms were performed at the saturated concentration of IMP (substrate) and variation concentrations of NAD+ (cofactor) in the activity buffer solution containing 10 mM Tris-HCl (PH:8), 1mM DTT, 5 mM EDTA and 50 mM KCl. Production of the NADH was monitored at 340 nm using UV-visible spectrophotometer. Kinetic parameters (Km,Vmax) of the mouse IMPDH1 isoforms, determined by Line Weaver-Burk approach, were noticeably different together. Our experiments indicated that enzyme activity of the mouse retinal IMPDH1 isoforms, with higher Vmax and Km relative to the canonical isoform, inhibited at high concentration of the cofactor. This observation might reflect the impact of the terminal amino acid extensions on the enzyme active site.

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برومند، نیلوفر، 1398، Terminal amino acid extensions impress the retinal IMPDH1 active site، چهارمين كنفرانس ملي علوم پروتئيني و پپتيدي، https://conf.ui.ac.ir/fa/archive_index.php?c=pps4&aid=1505322