Mutations in the retinal inosine monophosphate dehydrogenase1 (IMPDH1) gene is believed to be one cause of retinitis pigmentosa (RP). The main structural difference between the mutation-susceptible retinal isoforms with canonical one resides in the C- and N-terminal extensions. There are limited studies on the structure and function of terminal peptide extensions of the IMPDH1 retinal isoforms. Using recombinant murine IMPDH1 (mH1), we evaluated the kinetics of the retinal isoforms along with inhibition by some of the purine nucleotides. Molecular modeling tools were also applied to study the probable effect(s) of the terminal peptide tails on the function of the retinal isoforms. Molecular dynamic simulations indicated the possible impact of the end-terminal segments on the enzyme function through interactions with the enzyme's finger domain, affecting its critical pseudo barrel structure. The higher experimentally-determined Km and Ki values of the retinal mIMPDH1 (546) and mIMPDH1 (603) relative to that of the canonical isoform, mIMPDH1 (514), might clearly be due to these interactions. Furthermore and despite of the canonical isoform, the retinal isoforms of mH1 exhibited no NAD+ substrate inhibition. The resent data would certainly provide the ground for future evaluation of the physiological significance of these variations.

中文翻译：

---

小鼠视网膜IMPDH1亚型的C / N端延伸的功能影响：动力学评估。

视网膜肌苷单磷酸脱氢酶1（IMPDH1）基因的突变被认为是色素性视网膜炎（RP）的原因之一。具有典型突变的易感性视网膜同工型之间的主要结构差异在于C和N端延伸。关于IMPDH1视网膜同工型的末端肽延伸的结构和功能的研究很少。使用重组鼠IMPDH1（mH1），我们评估了视网膜同工型的动力学以及一些嘌呤核苷酸的抑制作用。分子建模工具也被用于研究末端肽尾对视网膜同工型功能的可能影响。分子动力学模拟表明，末端末端片段可能通过与酶的指状结构域相互作用而对酶的功能产生影响，影响其关键的伪桶结构。相对于经典同工型mIMPDH1（514），视网膜mIMPDH1（546）和mIMPDH1（603）的实验确定的Km和Ki值较高。此外，尽管存在典型的同工型，但mH1的视网膜同工型没有NAD +底物抑制作用。最近的数据肯定会为将来评估这些变异的生理学意义提供基础。mH1的视网膜同种型没有NAD +底物抑制。最近的数据肯定会为将来评估这些变异的生理学意义提供基础。mH1的视网膜同种型没有NAD +底物抑制。最近的数据肯定会为将来评估这些变异的生理学意义提供基础。