Open AccessCrystal structure of chloramphenicol-metabolizing enzyme EstDL136 from a metagenome
Author(s) -
Sang-Hoon Kim,
Pyoyoon Kang,
Keetae Han,
Seon-Woo Lee,
Sangkee Rhee
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0210298
Subject(s) - metagenomics , catalytic triad , active site , computational biology , biology , hydrolase , binding site , substrate (aquarium) , sequence alignment , structural similarity , enzyme , genetics , peptide sequence , biochemistry , gene , ecology
Metagenomes often convey novel biological activities and therefore have gained considerable attention for use in biotechnological applications. Recently, metagenome-derived EstDL136 was found to possess chloramphenicol (Cm)-metabolizing features. Sequence analysis showed EstDL136 to be a member of the hormone-sensitive lipase (HSL) family with an Asp-His-Ser catalytic triad and a notable substrate specificity. In this study, we determined the crystal structures of EstDL136 and in a complex with Cm. Consistent with the high sequence similarity, the structure of EstDL136 is homologous to that of the HSL family. The active site of EstDL136 is a relatively shallow pocket that could accommodate Cm as a substrate as opposed to the long acyl chain substrates typical of the HSL family. Mutational analyses further suggested that several residues in the vicinity of the active site play roles in the Cm-binding of EstDL136. These results provide structural and functional insights into a metagenome-derived EstDL136.