title: Structural and mutational studies on the unusual substrate specificity of meso-diaminopimelate dehydrogenase from Symbiobacterium thermophilum.
abstract: Wild-type meso-diaminopimelate dehydrogenase (DAPDH) is usually specific to the native substrate, meso-2,6-diaminopimelate. Recently, a DAPDH from Symbiobacterium thermophilum (StDAPDH) was found to exhibit expanded substrate specificity. As such, its crystal structures in apo form and in complex with NADP(+) and both NADPH and meso-DAP were investigated to reveal the structural basis of its unique catalytic properties. Structural analysis results show that StDAPDH should prefer an ordered kinetic catalytic mechanism. A second substrate entrance tunnel with Met152 at its bottleneck was found, through which pyruvate/D-alanine might bind and enter the catalytic cavity, providing some structural insights into its high activity toward pyruvate. The side chain of Met152 might interact with Asp92 and Asn253, thus affecting the domain motion and catalysis. These results offer useful information for understanding the unique catalytic properties of StDAPDH and guiding further engineering of this enzyme.
authors: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 Xi Qi Dao, Tianjin Airport Economic Area, Tianjin 300308 (China).
authors: Weidong
authors: W
authors: Liu
authors: Zhe
authors: Z
authors: Li
authors: Chun-Hsiang
authors: CH
authors: Huang
authors: Rey-Ting
authors: RT
authors: Guo
authors: Leiming
authors: L
authors: Zhao
authors: Dalong
authors: D
authors: Zhang
authors: Xi
authors: X
authors: Chen
authors: Qiaqing
authors: Q
authors: Wu
authors: Dunming
authors: D
authors: Zhu
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020563:Gammaproteobacteria / Q000201:enzymology*; D008958:Models, Molecular; D016296:Mutagenesis; D009154:Mutation; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D000594:Amino Acid Oxidoreductases; C020032:diaminopimelate dehydrogenase
keywords: amination; enzyme catalysis; meso-diaminopimelate dehydrogenase; mutagenesis; protein structure