Schelp E, Worley S, Monzingo A F, Ernst S, Robertus J D
Institute of Cellular and Molecular Biology, Department of Chemistry and Biochemistry, University of Texas, Austin, TX, 78712, USA.
J Mol Biol. 2001 Mar 2;306(4):727-32. doi: 10.1006/jmbi.2000.4430.
Histidine decarboxylase (HDC) from Lactobacillus 30a produces histamine that is essential to counter waste acids, and to optimize cell growth. The HDC trimer is active at low pH and inactive at neutral to alkaline pH. We have solved the X-ray structure of HDC at pH 8 and revealed the novel mechanism of pH regulation. At high pH helix B is unwound, destroying the substrate binding pocket. At acid pH the helix is stabilized, partly through protonation of Asp198 and Asp53 on either side of the molecular interface, acting as a proton trap. In contrast to hemoglobin regulation, pH has a large effect on the tertiary structure of HDC monomers and relatively little or no effect on quaternary structure.
来自乳酸杆菌30a的组氨酸脱羧酶（HDC）产生组胺，组胺对于中和废酸以及优化细胞生长至关重要。HDC三聚体在低pH值下具有活性，而在中性至碱性pH值下无活性。我们解析了pH值为8时HDC的X射线结构，并揭示了pH调节的新机制。在高pH值下，螺旋B展开，破坏了底物结合口袋。在酸性pH值下，螺旋通过分子界面两侧的Asp198和Asp53质子化而部分稳定，起到质子陷阱的作用。与血红蛋白调节不同，pH值对HDC单体的三级结构有很大影响，而对四级结构影响相对较小或没有影响。
