Detailed Mechanism for AmtB Conducting NH₄⁺/NH₃: Molecular Dynamics Simulations

详细信息    查看全文

• 作者：Huaiyu Yang ; Yechun Xu ; Weiliang Zhu ; Kaixian Chen ; Hualiang Jiang
• 刊名：Biophysical Journal
• 出版年：2007
• 出版时间：1 February 2007
• 年：2007
• 卷：92
• 期：3
• 页码：877-885
• 全文大小：1120 K

文摘

The mechanism by which the ammonium transporter, AmtB, conducts into the cytoplasm was investigated using conventional molecular dynamics (MD) simulations. These simulations revealed that the neutral molecule, NH₃, passes automatically through the channel upon its arrival at the Am2 site and that the function of the channel as a one-way valve for passage of NH₃ is not determined by the cytoplasmic exit gate but, rather, by the periplasmic entrance gate of the channel. The NH₃, produced by deprotonation of at the entrance gate, is spontaneously conveyed to the central region of the channel via a hydrogenbond network comprising His-168, His-318, Tyr-32, and the NH₃ molecule. Finally, the NH₃ molecule exits the channel through the exit gate formed by Phe-31, Ile-266, Val-314, and His-318. In addition, Ser-263 is shown to play a critical role in the final stages, acting as a pivoting arm to shunt the NH₃ molecule from the cytoplasmic exit gate of the channel out into the cytoplasm. This finding is further supported by another simulation which shows that NH₃ fails to be translocated through the channel formed by the Ser-263–Ala mutation. Thus, this study casts new insights on the mechanism of AmtB-mediated passage of NH₃ across cellular membranes.