title: Crystal structures of S-adenosylhomocysteine hydrolase from the thermophilic bacterium Thermotoga maritima.
abstract: S-adenosylhomocysteine (SAH) hydrolase catalyzes the reversible hydrolysis of SAH into adenosine and homocysteine by using NAD(+) as a cofactor. The enzyme from Thermotoga maritima (tmSAHH) has great potentials in industrial applications because of its hyperthermophilic properties. Here, two crystal structures of tmSAHH in complex with NAD(+) show both open and closed conformations despite the absence of bound substrate. Each subunit of the tetrameric enzyme is composed of three domains, namely the catalytic domain, the NAD(+)-binding domain and the C-terminal domain. The NAD(+) binding mode is clearly observed and a substrate analogue can also be modeled into the active site, where two cysteine residues in mesophilic enzymes are replaced by serine and threonine in tmSAHH. Notably, the C-terminal domain of tmSAHH lacks the second loop region of mesophilic SAHH, which is important in NAD(+) binding, and thus exposes the bound cofactor to the solvent. The difference explains the higher NAD(+) requirement of tmSAHH because of the reduced affinity. Furthermore, the feature of missing loop is consistently observed in thermophilic bacterial and archaeal SAHHs, and may be related to their thermostability.
authors: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
authors: Yingying
authors: Y
authors: Zheng
authors: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
authors: Chun-Chi
authors: CC
authors: Chen
authors: Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
authors: Tzu-Ping
authors: TP
authors: Ko
authors: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
authors: Xiansha
authors: X
authors: Xiao
authors: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
authors: Yunyun
authors: Y
authors: Yang
authors: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
authors: Chun-Hsiang
authors: CH
authors: Huang
authors: Biofuels Institute, School of Environment, Jiangsu University, Zhenjiang 212013, China.
authors: Guojun
authors: G
authors: Qian
authors: Biofuels Institute, School of Environment, Jiangsu University, Zhenjiang 212013, China. Electronic address: weilanshao@gmail.com.
authors: Weilan
authors: W
authors: Shao
authors: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China. Electronic address: guo_rt@tib.cas.cn.
authors: Rey-Ting
authors: RT
authors: Guo
mesh_terms: D043383:Adenosylhomocysteinase / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D008958:Models, Molecular; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D020124:Thermotoga maritima / Q000201:enzymology*; D014961:X-Ray Diffraction
chemical_list: D009243:NAD; D043383:Adenosylhomocysteinase
keywords: C-terminal loop; Hyperthermophilic enzyme; NAD(+)-binding domain; S-adenosylhomocysteine hydrolase; Thermostability