Meredith D, Price R A
Department of Physiology, Anatomy & Genetics, Le Gros Clark Building, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK.
J Membr Biol. 2006;213(2):79-88. doi: 10.1007/s00232-006-0876-6. Epub 2007 Apr 6.
The proton-coupled uptake of di- and tri-peptides is the major route of dietary nitrogen absorption in the intestine and of reabsorption of filtered protein in the kidney. In addition, the transporters involved, PepT1 (SLC15a1) and PepT2 (SLC15a2), are responsible for the uptake and tissue distribution of a wide range of pharmaceutically important compounds, including beta-lactam antibiotics, angiotensin-converting enzyme inhibitors, anti-cancer and anti-viral drugs. PepT1 and PepT2 are large proteins, with over 700 amino acids, and to date there are no reports of their crystal structures, nor of those of related proteins from lower organisms. Therefore there is virtually no information about the protein 3-D structure, although computer-based approaches have been used to both model the transmembrane domain (TM) layout and to produce a substrate binding template. These models will be discussed, and a new one proposed from homology modeling rabbit PepT1 to the recently crystallized bacterial transporters LacY and GlpT. Understanding the mechanism by which PepT1 and PepT2 bind and transport their substrates is of great interest to researchers, both in academia and in the pharmaceutical industries.
二肽和三肽的质子偶联摄取是肠道中膳食氮吸收以及肾脏中滤过蛋白质重吸收的主要途径。此外，所涉及的转运蛋白PepT1（SLC15a1）和PepT2（SLC15a2）负责多种具有重要药学意义的化合物的摄取和组织分布，包括β-内酰胺抗生素、血管紧张素转换酶抑制剂、抗癌和抗病毒药物。PepT1和PepT2是大蛋白，含有超过700个氨基酸，迄今为止，尚无关于它们的晶体结构的报道，也没有来自低等生物的相关蛋白晶体结构的报道。因此，尽管已使用基于计算机的方法来模拟跨膜结构域（TM）布局并生成底物结合模板，但实际上几乎没有关于蛋白质三维结构的信息。将讨论这些模型，并提出一个基于兔PepT1与最近结晶的细菌转运蛋白LacY和GlpT的同源建模的新模型。了解PepT1和PepT2结合并转运其底物的机制，无论是对于学术界还是制药行业的研究人员都具有极大的兴趣。
