Eleven missense mutations have been describe in human triosephosphate isomerase (TPI), affecting its catalytic function. Several of these mutations generate triosephosphate isomerase deficiency, the consequences of which can in some cases be lethal. The missense F240L mutation was found in a Hungarian patient showing symptoms of chronic hemolytic anemia and neuromuscular dysfunction. In vitro studies using a recombinant version of this mutant showed that it affects kinetic parameters, thermal stability and dimeric stability. Using X-ray crystal structures, the present paper describes how this mutation affected the flexibility of catalytic residues K13 and part of the (β/α) 8-barrel fold facing the dimeric interface in the TPI.

人三磷酸磷酸异构酶（TPI）中已经描述了11个错义突变，影响其催化功能。其中一些突变会导致磷酸三磷酸异构酶缺乏症，在某些情况下，其后果可能是致命的。在匈牙利患者中发现了错义的F240L突变，显示出慢性溶血性贫血和神经肌肉功能障碍的症状。使用该突变体的重组体进行的体外研究表明，它会影响动力学参数，热稳定性和二聚体稳定性。本文使用X射线晶体结构，描述了这种突变如何影响催化残基K13的柔性以及（TPA）中面向二聚体界面的部分（β/α）8桶折叠。