Frank René A W, Titman Christopher M, Pratap J Venkatesh, Luisi Ben F, Perham Richard N
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, UK.
Science. 2004 Oct 29;306(5697):872-6. doi: 10.1126/science.1101030.
Thiamine diphosphate (ThDP) is used as a cofactor in many key metabolic enzymes. We present evidence that the ThDPs in the two active sites of the E1 (EC 1.2.4.1) component of the pyruvate dehydrogenase complex communicate over a distance of 20 angstroms by reversibly shuttling a proton through an acidic tunnel in the protein. This "proton wire" permits the co-factors to serve reciprocally as general acid/base in catalysis and to switch the conformation of crucial active-site peptide loops. This synchronizes the progression of chemical events and can account for the oligomeric organization, conformational asymmetry, and "ping-pong" kinetic properties of E1 and other thiamine-dependent enzymes.
硫胺素二磷酸（ThDP）在许多关键代谢酶中用作辅因子。我们提供的证据表明，丙酮酸脱氢酶复合体E1（EC 1.2.4.1）组分的两个活性位点中的ThDP通过在蛋白质中的酸性通道可逆地穿梭质子，在20埃的距离上进行通信。这种“质子线”允许辅因子在催化过程中相互作为通用酸/碱，并切换关键活性位点肽环的构象。这使化学事件的进程同步，并可以解释E1和其他硫胺素依赖性酶的寡聚组织、构象不对称性和“乒乓”动力学性质。
