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Structural and Mutational Studies on the Unusual Substrate Specificity of meso ‐Diaminopimelate Dehydrogenase from Symbiobacterium thermophilum
Author(s) -
Liu Weidong,
Li Zhe,
Huang ChunHsiang,
Guo ReyTing,
Zhao Leiming,
Zhang Dalong,
Chen Xi,
Wu Qiaqing,
Zhu Dunming
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201300691
Subject(s) - substrate (aquarium) , chemistry , catalysis , stereochemistry , protein structure , substrate specificity , oxidoreductase , dehydrogenase , structural biology , enzyme , biochemistry , biology , ecology
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.