Pseudoradicular and radicular low-back pain: How to diagnose clinically?
- 作者：Koen Van Boxem ; Jan Van Zundert ; Jan Van Zundert ; Jacob Patijn ; Maarten van Kleef
- 关键词：Mucopolysaccharidosis type VI ; Maroteaux– ; Lamy syndrome ; N-Acetylgalactosamine-4-sulfatase ; Gene mutation ; Protein structure
- 刊名：Pain
- 出版年：2008
- 期刊代码：214_03043959
- 类别：med
- 出版时间：April 2008
- 卷：135
- 期：3
- 页码：311-312
- 文件大小：70 K
摘要
To elucidate the basis of mucopolysaccharidosis type VI (MPS VI) from the point of view of enzyme structure, we built structural models of mutant N-acetylgalactosamine-4-sulfatase (4S) resulting from 34 missense mutations (17 severe and 17 attenuated), and analyzed the influence of each amino acid replacement on the structure by calculating the number of atoms affected. Then, we calculated the average of solvent-accessible surface area value of the residues for which a substitution was identified in the severe MPS VI group and compared it with that in the attenuated MPS VI group. In the severe MPS VI group, the number of atoms influenced by a mutation was generally larger than that in the attenuated MPS VI group in both the main chain and the side chain, and residues associated with the mutations found in the severe MPS VI group tended to be less solvent-accessible than those in the attenuated MPS VI group. Furthermore, we analyzed the structural changes in 4S caused by six amino acid substitutions, for which the expressed proteins have been characterized, by means of color imaging. The results revealed that R95Q, G144R, H393P, and C521Y cause large structural changes, and that they are associated with the severe phenotype. On the other hand, G137V and Y210C are thought to cause small structural changes in a limited region resulting in the attenuated phenotype. Structural study is useful for elucidating the basis of MPS VI and predicting the influence of amino acid substitutions on clinical outcome, although there are a couple of exceptional cases.