6WQ1

Eukaryotic LanCL2 protein

Summary for 6WQ1

• Entry DOI: 10.2210/pdb6wq1/pdb
• Descriptor: LanC-like protein 2, ZINC ION (3 entities in total)
• Functional Keywords: lanthipeptide, cyclase, zinc, biosynthetic protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 203954.73

Authors

Nair, S.K.,Garg, N. (deposition date: 2020-04-28, release date: 2021-05-05, Last modification date: 2023-10-18)

Primary citation

Lai, K.Y.,Galan, S.R.G.,Zeng, Y.,Zhou, T.H.,He, C.,Raj, R.,Riedl, J.,Liu, S.,Chooi, K.P.,Garg, N.,Zeng, M.,Jones, L.H.,Hutchings, G.J.,Mohammed, S.,Nair, S.K.,Chen, J.,Davis, B.G.,van der Donk, W.A.
LanCLs add glutathione to dehydroamino acids generated at phosphorylated sites in the proteome.
Cell, 184:2680-2695.e26, 2021

PubMed Abstract: Enzyme-mediated damage repair or mitigation, while common for nucleic acids, is rare for proteins. Examples of protein damage are elimination of phosphorylated Ser/Thr to dehydroalanine/dehydrobutyrine (Dha/Dhb) in pathogenesis and aging. Bacterial LanC enzymes use Dha/Dhb to form carbon-sulfur linkages in antimicrobial peptides, but the functions of eukaryotic LanC-like (LanCL) counterparts are unknown. We show that LanCLs catalyze the addition of glutathione to Dha/Dhb in proteins, driving irreversible C-glutathionylation. Chemo-enzymatic methods were developed to site-selectively incorporate Dha/Dhb at phospho-regulated sites in kinases. In human MAPK-MEK1, such "elimination damage" generated aberrantly activated kinases, which were deactivated by LanCL-mediated C-glutathionylation. Surveys of endogenous proteins bearing damage from elimination (the eliminylome) also suggest it is a source of electrophilic reactivity. LanCLs thus remove these reactive electrophiles and their potentially dysregulatory effects from the proteome. As knockout of LanCL in mice can result in premature death, repair of this kind of protein damage appears important physiologically.

PubMed: 33932340
DOI: 10.1016/j.cell.2021.04.001

Experimental method

X-RAY DIFFRACTION (2.295 Å)