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Structural insights into the ligand recognition and catalysis of the key aminobutanoyltransferase CntL in staphylopine biosynthesis
Author(s) -
Luo Zhiteng,
Luo Siting,
Ju Yingchen,
Ding Peng,
Xu Jun,
Gu Qiong,
Zhou Huihao
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202002287rr
Subject(s) - ligand (biochemistry) , biosynthesis , key (lock) , chemistry , biology , biochemistry , ecology , gene , receptor
Staphylopine (StP) and other nicotianamine‐like metallophores are crucial for many pathogens to acquire the transition metals from hosts during invasion. CntL from Staphylococcus aureus ( Sa CntL) catalyzes the condensation of the 2‐aminobutyrate (Ab) moiety of S‐adenosylmethionine (SAM) with D‐histidine in the biosynthesis of StP. Here, we report the crystal structures of Sa CntL in complex with either SAM or two products. The structure of Sa CntL consists of an N‐terminal four‐helix bundle (holding catalytic residue E84) and a C‐terminal Rossmann fold (binding the substrates). The sequence connecting the N‐ and C‐terminal domains (N‐C linker) in Sa CntL was found to undergo conformational alternation between open and closed states. Our structural and biochemical analyses suggested that this intrinsically dynamic interdomain linker forms an additional structural module that plays essential roles in ligand diffusion, recognition, and catalysis. We confirmed that Sa CntL stereoselectively carries out the catalysis of D‐His but not its enantiomer, L‐His, and we found that the N‐C linker and active site of Sa CntL could accommodate both enantiomers. Sa CntL is likely able to bind L‐His without catalysis, and as a result, L‐His could show inhibitory effects toward Sa CntL. These findings provide critical structural and mechanistic insights into CntL, which facilitates a better understanding of the biosynthesis of nicotianamine‐like metallophores and the discovery of inhibitors of this process.