Xiao Jingfa, Guo Zongru, Guo Yanshen, Chu Fengming, Sun Piaoyang
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
J Mol Graph Model. 2006 Nov;25(3):289-95. doi: 10.1016/j.jmgm.2006.01.001. Epub 2006 Feb 20.
Phosphomannose isomerase is a zinc metalloenzyme that catalyzes the reversible isomerization of mannose-6-phosphate and fructose-6-phosphate, and the three-dimensional (3D) structure of human phosphomannose isomerase has not been reported. In order to understand the catalytic mechanism, the 3D structure of the protein is built by using homology modeling based on the known crystal structure of mannose-6-phosphate isomerase from (PDB code 1PMI). The model structure is further refined by energy minimization and molecular dynamics methods. The mannose-6-phosphate-enzyme complex is developed by molecular docking and the key residues involved in the ligand binding are determined, which will facilitate the understanding of the action mode of the ligands and guide further genetic studies. Our results suggest a hydride transfer mechanism of alpha-hydrogen between the C1 and C2 positions but do not support the cis-enediol mechanism. The detailed mechanism involves, on one side, Zn2+ mediating the movement of a proton between O1 and O2, and, on the other side, the hydrophobic environment formed in part by Tyr278 promoting transfer of a hydride ion.
磷酸甘露糖异构酶是一种锌金属酶，可催化甘露糖-6-磷酸和果糖-6-磷酸之间的可逆异构化反应，而人磷酸甘露糖异构酶的三维（3D）结构尚未见报道。为了解其催化机制，基于来自（蛋白质数据银行代码1PMI）的甘露糖-6-磷酸异构酶的已知晶体结构，通过同源建模构建了该蛋白质的3D结构。通过能量最小化和分子动力学方法进一步优化模型结构。通过分子对接构建了甘露糖-6-磷酸-酶复合物，并确定了参与配体结合的关键残基，这将有助于理解配体的作用模式并指导进一步的遗传学研究。我们的结果表明了C1和C2位置之间α-氢的氢化物转移机制，但不支持顺式烯二醇机制。详细机制一方面涉及Zn2+介导质子在O1和O2之间移动，另一方面涉及部分由Tyr278形成的疏水环境促进氢化物离子转移。
