Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Site-Specific Histidine Aza-Michael Addition in Proteins Enabled by a Ferritin-Based Metalloenzyme.
Journal, issue, pages	J Am Chem Soc, Vol. 146, Issue 49, Page 33309-33315, Year 2024
Publish date	Dec 11, 2024
Authors	Jo-Chu Tsou / Chun-Ju Tsou / Chun-Hsiung Wang / An-Li A Ko / Yi-Hui Wang / Huan-Hsuan Liang / Jia-Cheng Sun / Kai-Fa Huang / Tzu-Ping Ko / Shu-Yu Lin / Yane-Shih Wang /
PubMed Abstract	Histidine modifications of proteins are broadly based on chemical methods triggering N-substitution reactions such as aza-Michael addition at histidine's moderately nucleophilic imidazole side chain. ...Histidine modifications of proteins are broadly based on chemical methods triggering N-substitution reactions such as aza-Michael addition at histidine's moderately nucleophilic imidazole side chain. While recent studies have demonstrated chemoselective, histidine-specific modifications by further exploiting imidazole's electrophilic reactivity to overcome interference from the more nucleophilic lysine and cysteine, achieving site-specific histidine modifications remains a major challenge due to the absence of spatial control over chemical processes. Herein, through X-ray crystallography and cryo-electron microscopy structural studies, we describe the rational design of a nature-inspired, noncanonical amino-acid-incorporated, human ferritin-based metalloenzyme that is capable of introducing site-specific post-translational modifications (PTMs) to histidine in peptides and proteins. Specifically, chemoenzymatic aza-Michael additions on single histidine residues were carried out on eight protein substrates ranging from 10 to 607 amino acids including the insulin peptide hormone. By introducing an insulin-targeting peptide into our metalloenzyme, we further directed modifications to be carried out site-specifically on insulin's B-chain histidine 5. The success of this biocatalysis platform outlines a novel approach in introducing residue- and, moreover, site-specific post-translational modifications to peptides and proteins, which may further enable reactions to be carried out .
External links	J Am Chem Soc / PubMed:39499210 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	1.73 - 2.28 Å
Structure data	61726 9jqb EMDB-61726, PDB-9jqb: Cryo-EM structure of ferritin variant R63BrThA/E67BrThA Method: EM (single particle) / Resolution: 1.78 Å 61727 9jqc EMDB-61727, PDB-9jqc: Cryo-EM structure of ferritin variant R63BrThA/E67BrThA with Cu(II) Method: EM (single particle) / Resolution: 1.73 Å 61728 9jqd EMDB-61728, PDB-9jqd: Cryo-EM structure of ferritin variant R63MeH/R67MeH Method: EM (single particle) / Resolution: 1.81 Å 61729 9jqe EMDB-61729, PDB-9jqe: Cryo-EM structure of ferritin variant R63MeH/R67MeH with Cu(II) Method: EM (single particle) / Resolution: 1.83 Å PDB-9jiu: Ferritin mutant R63MeHis Method: X-RAY DIFFRACTION / Resolution: 2.28 Å
Chemicals	ChemComp-NA: Unknown entry ChemComp-P6G: HEXAETHYLENE GLYCOL / precipitantYM ChemComp-HOH: WATER ChemComp-CU: COPPER (II) ION ChemComp-FE*: Unknown entry
Source	homo sapiens (human)
Keywords	METAL BINDING PROTEIN / 3-methyl-histidine / apo-form / human heavy chain ferritin / Cryo-EM / ferritin variant / non-canonical amino acid / L-2-(5-Bromothienyl)alanine (BrThA) / metalloenzyme / copper / H-N-3-Methyl-L-histidine(MeH)