Liu Jing-Yuan, Hurley Thomas D
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Int J Biochem Mol Biol. 2011;2(2):111-8.
Thiamin pyrophosphokinase (TPK) transfers a pyrophosphate group from ATP to the hydroxyl group of thiamin and produces thiamin pyrophosphate (TPP). TPP is the cofactor of metabolically important enzymes such as pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, branched-chain α-keto acid dehydrogenase, transketolase and 2-hydroxyphytanoyl-CoA lyase. Thiamin deficiency results in Wernike-Korsakof Syndrome (WKS) due to neurological disorder and wet beriberi, a potentially fatal cardiovascular disease. Mouse TPK associates as a dimer revealed by previous solved crystallographic structures. In this study, we report mouse TPK complexed with TPP-Mg(2+) and thiamin -Mg(2+), respectively, in a new crystal form. In these two structures, four mouse TPK molecules were found in each asymmetric unit. Although we cannot rule out this tetramer form can be an artifact from crystal packing, mouse TPK tetramer has a more closed ATP binding pocket and has the potential to provide specific interactions between mouse TPK and ATP compared with the previous dimeric structure and is likely to be an active form.
硫胺素焦磷酸激酶（TPK）将ATP的一个焦磷酸基团转移到硫胺素的羟基上，生成硫胺素焦磷酸（TPP）。TPP是代谢中重要酶的辅酶，如丙酮酸脱氢酶、α-酮戊二酸脱氢酶、支链α-酮酸脱氢酶、转酮醇酶和2-羟基植烷酰辅酶A裂解酶。硫胺素缺乏会导致韦尼克-科尔萨科夫综合征（WKS），原因是神经紊乱以及湿性脚气病，一种潜在的致命心血管疾病。先前解析的晶体结构显示小鼠TPK以二聚体形式存在。在本研究中，我们报道了小鼠TPK分别与TPP-Mg(2+)和硫胺素-Mg(2+)以新的晶体形式形成复合物。在这两种结构中，每个不对称单元中发现有四个小鼠TPK分子。尽管我们不能排除这种四聚体形式可能是晶体堆积造成的假象，但与先前的二聚体结构相比，小鼠TPK四聚体具有更封闭的ATP结合口袋，有可能提供小鼠TPK与ATP之间的特异性相互作用，并且可能是一种活性形式。
