Structural Analysis Reveals the Substrate‐Binding Mechanism for the Expanded Substrate Specificity of Mutant meso‐Diaminopimelate Dehydrogenase. Issue 6 (6th March 2015)

• Record Type: Journal Article
• Authors: Liu, Weidong; Guo, Rey‐Ting; Chen, Xi; Li, Zhe; Gao, Xiuzhen; Huang, Chun‐Hsiang; Wu, Qiaqing; Feng, Jinhui; Zhu, Dunming
• Is Part Of: Chembiochem. Volume 16:Issue 6(2015)
• Page Start: 924
• Page End: 929
• Publication Date: 2015-03-06
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201402632
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>A <italic>meso</italic>‐diaminopimelate dehydrogenase (DAPDH) from <italic>Clostridium tetani</italic> E88 (CtDAPDH) was found to have low activity toward the <sc>D</sc>‐amino acids other than its native substrate. Site‐directed mutagenesis similar to that carried out on the residues mutated by Vedha‐Peters et al. resulted in a mutant enzyme with highly improved catalytic ability for the synthesis of <sc>D</sc>‐amino acids. The crystal structures of the CtDAPDH mutant in apo form and in complex with <italic>meso</italic>‐diaminopimelate (<italic>meso</italic>‐DAP), <sc>D</sc>‐leucine (<sc>D</sc>‐leu), and 4‐methyl‐2‐oxopentanoic acid (MOPA) were solved. <italic>meso</italic>‐DAP was found in an area outside the catalytic cavity; this suggested a possible two‐step substrate‐binding mechanism for <italic>meso</italic>‐DAP. <sc>D</sc>‐leu and MOPA each bound both to Leu154 and to Gly155 in the open form of CtDAPDH, and structural analysis revealed the molecular basis for the expanded substrate specificity of the mutant <italic>meso</italic>‐diaminopimelate dehydrogenases.</p> </abstract>