Calcium in PDB 7vnn: Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem

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>>> Page 1 <<< Page 2, Binding sites: 11 - 20; Page 3, Binding sites: 21 - 21;

Binding sites:

The binding sites of Calcium atom in the Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem (pdb code 7vnn). This binding sites where shown within 5.0 Angstroms radius around Calcium atom.
In total 21 binding sites of Calcium where determined in the Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem, PDB code: 7vnn:
Jump to Calcium binding site number: 1; 2; 3; 4; 5; 6; 7; 8; 9; 10;

Calcium binding site 1 out of 21 in the Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem


Mono view


Stereo pair view

A full contact list of Calcium with other atoms in the Ca binding site number 1 of Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem within 5.0Å range: probe atom residue distance (Å) B Occ A:Ca901 b:30.7 occ:1.00 O A:ASN260 2.4 30.3 1.0 OD2 A:ASP222 2.4 35.0 1.0 O A:GLU263 2.4 29.3 1.0 OD2 A:ASP273 2.5 28.4 1.0 OD2 A:ASP224 2.5 34.2 1.0 OE1 A:GLU231 2.6 31.4 1.0 OE2 A:GLU231 3.0 31.4 1.0 CD A:GLU231 3.2 31.4 1.0 CG A:ASP273 3.5 28.4 1.0 C A:GLU263 3.6 29.3 1.0 CG A:ASP224 3.6 34.2 1.0 C A:ASN260 3.6 30.3 1.0 CG A:ASP222 3.6 35.0 1.0 CB A:ASP273 4.0 28.4 1.0 CA A:SER264 4.1 29.4 1.0 OG1 A:THR266 4.2 26.7 1.0 OD1 A:ASP224 4.2 34.2 1.0 CA A:TYR261 4.2 31.7 1.0 OG A:SER259 4.2 28.1 1.0 N A:SER264 4.3 29.4 1.0 OD1 A:ASP222 4.3 35.0 1.0 N A:TYR261 4.4 31.7 1.0 C A:SER264 4.5 29.4 1.0 CB A:SER259 4.5 28.1 1.0 N A:GLU263 4.5 29.3 1.0 CA A:CA902 4.6 36.4 1.0 O A:SER264 4.6 29.4 1.0 OD1 A:ASP273 4.6 28.4 1.0 C A:TYR261 4.6 31.7 1.0 N A:ASN260 4.6 30.3 1.0 CG A:GLU231 4.7 31.4 1.0 CB A:ASP224 4.7 34.2 1.0 CA A:ASN260 4.7 30.3 1.0 CB A:ASP222 4.7 35.0 1.0 CA A:GLU263 4.7 29.3 1.0 O A:TYR261 5.0 31.7 1.0

Calcium binding site 2 out of 21 in the Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem


Mono view


Stereo pair view

A full contact list of Calcium with other atoms in the Ca binding site number 2 of Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem within 5.0Å range: probe atom residue distance (Å) B Occ A:Ca902 b:36.4 occ:1.00 OD1 A:ASP222 2.3 35.0 1.0 O A:ILE226 2.3 32.3 1.0 OE2 A:GLU231 2.3 31.4 1.0 OD1 A:ASP220 2.4 37.1 1.0 OD1 A:ASP224 2.5 34.2 1.0 CG A:ASP222 3.2 35.0 1.0 OD1 A:ASP228 3.4 34.1 1.0 OD2 A:ASP222 3.4 35.0 1.0 CG A:ASP224 3.5 34.2 1.0 CD A:GLU231 3.5 31.4 1.0 C A:ILE226 3.5 32.3 1.0 CG A:ASP220 3.6 37.1 1.0 OD2 A:ASP224 3.8 34.2 1.0 CG A:GLU231 4.2 31.4 1.0 OD2 A:ASP220 4.2 37.1 1.0 O A:TYR261 4.2 31.7 1.0 C A:PRO227 4.3 33.0 1.0 CA A:ILE226 4.3 32.3 1.0 N A:ILE226 4.3 32.3 1.0 CB A:ILE226 4.3 32.3 1.0 N A:ASP228 4.4 34.1 1.0 CA A:ASP220 4.4 37.1 1.0 O A:PRO227 4.4 33.0 1.0 N A:ASP224 4.5 34.2 1.0 N A:ASP222 4.5 35.0 1.0 OE1 A:GLU231 4.5 31.4 1.0 N A:PRO227 4.5 33.0 1.0 CA A:CA901 4.6 30.7 1.0 N A:THR221 4.6 38.2 1.0 CB A:ASP220 4.6 37.1 1.0 CA A:PRO227 4.6 33.0 1.0 CG A:ASP228 4.6 34.1 1.0 CB A:ASP222 4.6 35.0 1.0 CA A:ASP228 4.7 34.1 1.0 CA A:TYR261 4.7 31.7 1.0 N A:ASN223 4.7 37.3 1.0 CB A:ASP224 4.8 34.2 1.0 C A:ASP220 4.8 37.1 1.0 C A:TYR261 4.9 31.7 1.0 CB A:TYR261 4.9 31.7 1.0 CA A:ASP222 5.0 35.0 1.0

Calcium binding site 3 out of 21 in the Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem


Mono view


Stereo pair view

A full contact list of Calcium with other atoms in the Ca binding site number 3 of Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem within 5.0Å range: probe atom residue distance (Å) B Occ A:Ca903 b:65.9 occ:1.00 OG A:SER646 2.4 94.8 1.0 O A:GLN644 2.5 83.0 1.0 OD2 A:ASP623 2.6 80.4 1.0 O A:ASN621 2.7 71.7 1.0 OD1 A:ASP734 3.2 77.6 1.0 CB A:SER646 3.2 94.8 1.0 CG A:ASP623 3.2 80.4 1.0 OD1 A:ASP623 3.2 80.4 1.0 C A:GLN644 3.3 83.0 1.0 OD2 A:ASP734 3.4 77.6 1.0 N A:GLN644 3.7 83.0 1.0 CG A:ASP734 3.7 77.6 1.0 C A:ASN621 3.7 71.7 1.0 CA A:GLN644 3.8 83.0 1.0 CB A:GLN644 3.8 83.0 1.0 CB A:ASN621 3.9 71.7 1.0 N A:SER646 4.2 94.8 1.0 CA A:ASN621 4.2 71.7 1.0 CA A:SER646 4.3 94.8 1.0 OD1 A:ASN735 4.3 67.3 1.0 C A:GLY645 4.3 90.4 1.0 N A:GLY645 4.4 90.4 1.0 O A:GLY645 4.6 90.4 1.0 OE1 A:GLN644 4.6 83.0 1.0 CB A:ASP623 4.6 80.4 1.0 CG A:ASN621 4.7 71.7 1.0 ND2 A:ASN621 4.9 71.7 1.0 C A:LEU643 4.9 83.7 1.0 CA A:GLY645 4.9 90.4 1.0 N A:PHE622 4.9 77.7 1.0 O A:SER646 4.9 94.8 1.0

Calcium binding site 4 out of 21 in the Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem


Mono view


Stereo pair view

A full contact list of Calcium with other atoms in the Ca binding site number 4 of Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem within 5.0Å range: probe atom residue distance (Å) B Occ B:Ca901 b:28.4 occ:1.00 OD2 B:ASP224 2.4 32.1 1.0 O B:ASN260 2.4 29.5 1.0 O B:GLU263 2.4 27.8 1.0 OD2 B:ASP222 2.4 32.8 1.0 OD2 B:ASP273 2.6 25.7 1.0 OE1 B:GLU231 2.8 30.7 1.0 OE2 B:GLU231 3.0 30.7 1.0 CD B:GLU231 3.3 30.7 1.0 CG B:ASP224 3.3 32.1 1.0 CG B:ASP222 3.6 32.8 1.0 C B:GLU263 3.6 27.8 1.0 C B:ASN260 3.6 29.5 1.0 CG B:ASP273 3.7 25.7 1.0 OD1 B:ASP224 4.1 32.1 1.0 OD1 B:ASP222 4.2 32.8 1.0 CB B:ASP273 4.2 25.7 1.0 CA B:TYR261 4.2 30.3 1.0 CB B:ASP224 4.2 32.1 1.0 CA B:SER264 4.3 27.4 1.0 OG1 B:THR266 4.3 25.5 1.0 N B:TYR261 4.4 30.3 1.0 N B:SER264 4.4 27.4 1.0 N B:GLU263 4.4 27.8 1.0 OG B:SER259 4.5 29.7 1.0 O B:SER264 4.5 27.4 1.0 C B:TYR261 4.5 30.3 1.0 CA B:CA902 4.5 32.9 1.0 C B:SER264 4.6 27.4 1.0 CA B:GLU263 4.6 27.8 1.0 OD1 B:ASP273 4.7 25.7 1.0 CB B:ASP222 4.7 32.8 1.0 CA B:ASN260 4.7 29.5 1.0 N B:ASN260 4.8 29.5 1.0 CG B:GLU231 4.8 30.7 1.0 CB B:SER259 4.9 29.7 1.0 O B:TYR261 4.9 30.3 1.0 N B:LEU262 5.0 29.2 1.0

Calcium binding site 5 out of 21 in the Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem


Mono view


Stereo pair view

A full contact list of Calcium with other atoms in the Ca binding site number 5 of Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem within 5.0Å range: probe atom residue distance (Å) B Occ B:Ca902 b:32.9 occ:1.00 OD1 B:ASP222 2.4 32.8 1.0 O B:ILE226 2.4 30.8 1.0 OE2 B:GLU231 2.4 30.7 1.0 OD1 B:ASP224 2.5 32.1 1.0 OD1 B:ASP220 2.6 35.4 1.0 CG B:ASP222 3.3 32.8 1.0 CG B:ASP224 3.4 32.1 1.0 OD1 B:ASP228 3.5 32.4 1.0 C B:ILE226 3.6 30.8 1.0 CD B:GLU231 3.6 30.7 1.0 OD2 B:ASP222 3.6 32.8 1.0 CG B:ASP220 3.7 35.4 1.0 OD2 B:ASP224 3.8 32.1 1.0 O B:TYR261 4.1 30.3 1.0 CG B:GLU231 4.2 30.7 1.0 C B:PRO227 4.3 31.5 1.0 CA B:ASP220 4.3 35.4 1.0 N B:ASP222 4.4 32.8 1.0 N B:THR221 4.4 34.1 1.0 N B:ASP228 4.4 32.4 1.0 OD2 B:ASP220 4.4 35.4 1.0 N B:ILE226 4.4 30.8 1.0 CA B:ILE226 4.4 30.8 1.0 O B:PRO227 4.4 31.5 1.0 CA B:CA901 4.5 28.4 1.0 N B:PRO227 4.6 31.5 1.0 N B:ASP224 4.6 32.1 1.0 CA B:TYR261 4.6 30.3 1.0 CB B:ASP220 4.6 35.4 1.0 CB B:ILE226 4.6 30.8 1.0 CA B:PRO227 4.6 31.5 1.0 OE1 B:GLU231 4.6 30.7 1.0 C B:ASP220 4.6 35.4 1.0 CA B:ASP228 4.7 32.4 1.0 CB B:ASP222 4.7 32.8 1.0 CB B:ASP224 4.7 32.1 1.0 CG B:ASP228 4.7 32.4 1.0 C B:TYR261 4.8 30.3 1.0 CB B:TYR261 4.8 30.3 1.0 N B:ASN223 4.9 35.1 1.0 CA B:ASP222 5.0 32.8 1.0

Calcium binding site 6 out of 21 in the Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem


Mono view


Stereo pair view

A full contact list of Calcium with other atoms in the Ca binding site number 6 of Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem within 5.0Å range: probe atom residue distance (Å) B Occ B:Ca903 b:73.7 occ:1.00 OG B:SER646 2.4 89.4 1.0 OD2 B:ASP623 2.5 81.5 1.0 OD2 B:ASP734 2.5 77.3 1.0 OD1 B:ASP734 2.9 77.3 1.0 O B:GLN644 3.0 82.8 1.0 CG B:ASP734 3.1 77.3 1.0 N B:GLN644 3.1 82.8 1.0 O B:ASN621 3.2 72.7 1.0 C B:GLN644 3.5 82.8 1.0 CG B:ASP623 3.6 81.5 1.0 CB B:SER646 3.7 89.4 1.0 CA B:GLN644 3.7 82.8 1.0 OD1 B:ASP623 3.9 81.5 1.0 CB B:GLN644 4.0 82.8 1.0 OD1 B:ASN735 4.1 67.9 1.0 N B:LEU643 4.2 84.8 1.0 CB B:ASN621 4.2 72.7 1.0 C B:LEU643 4.2 84.8 1.0 N B:SER646 4.2 89.4 1.0 CB B:LEU643 4.2 84.8 1.0 OE1 B:GLN644 4.3 82.8 1.0 C B:ASN621 4.3 72.7 1.0 CA B:LEU643 4.4 84.8 1.0 N B:GLY645 4.4 88.8 1.0 O B:SER646 4.5 89.4 1.0 CA B:SER646 4.5 89.4 1.0 CB B:ASP734 4.5 77.3 1.0 CA B:ASN621 4.6 72.7 1.0 C B:GLY645 4.7 88.8 1.0 CD B:GLN644 4.7 82.8 1.0 CB B:ASP623 4.9 81.5 1.0 CG B:GLN644 4.9 82.8 1.0 C B:SER646 4.9 89.4 1.0 C B:GLY642 5.0 91.4 1.0 O B:ASP641 5.0 97.2 1.0 CG B:ASN735 5.0 67.9 1.0

Calcium binding site 7 out of 21 in the Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem


Mono view


Stereo pair view

A full contact list of Calcium with other atoms in the Ca binding site number 7 of Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem within 5.0Å range: probe atom residue distance (Å) B Occ C:Ca901 b:29.3 occ:1.00 O C:ASN260 2.4 29.6 1.0 OD2 C:ASP222 2.4 35.1 1.0 OD2 C:ASP224 2.5 35.4 1.0 O C:GLU263 2.5 29.7 1.0 OE1 C:GLU231 2.5 31.9 1.0 OD2 C:ASP273 2.6 28.1 1.0 OE2 C:GLU231 3.0 31.9 1.0 CD C:GLU231 3.1 31.9 1.0 CG C:ASP224 3.5 35.4 1.0 C C:ASN260 3.6 29.6 1.0 C C:GLU263 3.6 29.7 1.0 CG C:ASP273 3.7 28.1 1.0 CG C:ASP222 3.7 35.1 1.0 CB C:ASP273 4.1 28.1 1.0 OD1 C:ASP224 4.1 35.4 1.0 OG1 C:THR266 4.1 26.2 1.0 OG C:SER259 4.2 28.3 1.0 CA C:SER264 4.2 30.0 1.0 CA C:TYR261 4.3 31.3 1.0 O C:SER264 4.4 30.0 1.0 N C:SER264 4.4 30.0 1.0 OD1 C:ASP222 4.4 35.1 1.0 N C:TYR261 4.4 31.3 1.0 C C:SER264 4.5 30.0 1.0 CA C:CA902 4.6 37.7 1.0 CB C:ASP224 4.6 35.4 1.0 N C:GLU263 4.6 29.7 1.0 N C:ASN260 4.6 29.6 1.0 CG C:GLU231 4.6 31.9 1.0 CA C:ASN260 4.6 29.6 1.0 CB C:SER259 4.6 28.3 1.0 CB C:ASP222 4.7 35.1 1.0 CA C:GLU263 4.7 29.7 1.0 OD1 C:ASP273 4.7 28.1 1.0 C C:TYR261 4.7 31.3 1.0 C C:SER259 5.0 28.3 1.0

Calcium binding site 8 out of 21 in the Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem


Mono view


Stereo pair view

A full contact list of Calcium with other atoms in the Ca binding site number 8 of Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem within 5.0Å range: probe atom residue distance (Å) B Occ C:Ca902 b:37.7 occ:1.00 OD1 C:ASP222 2.3 35.1 1.0 O C:ILE226 2.3 33.8 1.0 OE2 C:GLU231 2.4 31.9 1.0 OD1 C:ASP220 2.5 41.0 1.0 OD1 C:ASP224 2.5 35.4 1.0 CG C:ASP222 3.2 35.1 1.0 OD2 C:ASP222 3.4 35.1 1.0 OD1 C:ASP228 3.5 35.8 1.0 CG C:ASP224 3.5 35.4 1.0 C C:ILE226 3.5 33.8 1.0 CD C:GLU231 3.6 31.9 1.0 CG C:ASP220 3.6 41.0 1.0 OD2 C:ASP224 3.9 35.4 1.0 N C:ILE226 4.2 33.8 1.0 CA C:ILE226 4.3 33.8 1.0 CG C:GLU231 4.3 31.9 1.0 C C:PRO227 4.3 34.2 1.0 CA C:ASP220 4.4 41.0 1.0 CB C:ILE226 4.4 33.8 1.0 OD2 C:ASP220 4.4 41.0 1.0 O C:PRO227 4.4 34.2 1.0 N C:ASP228 4.4 35.8 1.0 N C:ASP222 4.4 35.1 1.0 O C:TYR261 4.5 31.3 1.0 CB C:ASP220 4.5 41.0 1.0 N C:PRO227 4.5 34.2 1.0 OE1 C:GLU231 4.5 31.9 1.0 N C:ASP224 4.5 35.4 1.0 N C:THR221 4.5 35.5 1.0 CA C:CA901 4.6 29.3 1.0 CB C:ASP222 4.6 35.1 1.0 CA C:PRO227 4.6 34.2 1.0 CG C:ASP228 4.7 35.8 1.0 C C:ASP220 4.7 41.0 1.0 CA C:ASP228 4.7 35.8 1.0 N C:ASN223 4.8 38.1 1.0 CB C:ASP224 4.8 35.4 1.0 CA C:TYR261 4.8 31.3 1.0 CA C:ASP222 4.9 35.1 1.0

Calcium binding site 9 out of 21 in the Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem


Mono view


Stereo pair view

A full contact list of Calcium with other atoms in the Ca binding site number 9 of Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem within 5.0Å range: probe atom residue distance (Å) B Occ C:Ca903 b:71.1 occ:1.00 OG C:SER646 2.4 88.4 1.0 O C:GLN644 2.4 79.4 1.0 O C:ASN621 2.5 65.9 1.0 OD1 C:ASP734 2.6 75.8 1.0 OD2 C:ASP623 2.9 75.8 1.0 OD2 C:ASP734 3.0 75.8 1.0 CG C:ASP734 3.2 75.8 1.0 CB C:SER646 3.3 88.4 1.0 C C:GLN644 3.5 79.4 1.0 C C:ASN621 3.6 65.9 1.0 CG C:ASP623 3.7 75.8 1.0 N C:GLN644 3.7 79.4 1.0 CB C:ASN621 3.9 65.9 1.0 OD1 C:ASP623 3.9 75.8 1.0 CA C:ASN621 3.9 65.9 1.0 CA C:GLN644 3.9 79.4 1.0 CB C:GLN644 4.0 79.4 1.0 OD1 C:ASN735 4.0 65.7 1.0 N C:SER646 4.4 88.4 1.0 CA C:SER646 4.4 88.4 1.0 OE1 C:GLN644 4.5 79.4 1.0 N C:GLY645 4.6 83.6 1.0 C C:GLY645 4.6 83.6 1.0 CB C:ASP734 4.7 75.8 1.0 N C:PHE622 4.8 69.2 1.0 CB C:ASP623 4.8 75.8 1.0 CG C:ASN621 4.9 65.9 1.0 C C:LEU643 4.9 80.0 1.0 O C:GLY645 5.0 83.6 1.0 CD2 C:PHE622 5.0 69.2 1.0 CG C:ASN735 5.0 65.7 1.0

Calcium binding site 10 out of 21 in the Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem


Mono view


Stereo pair view

A full contact list of Calcium with other atoms in the Ca binding site number 10 of Complex Structure of Clostridioides Difficile Enzymatic Component (Cdta) and Binding Component (Cdtb) Pore with Long Stem within 5.0Å range: probe atom residue distance (Å) B Occ D:Ca901 b:29.8 occ:1.00 OD2 D:ASP222 2.3 38.1 1.0 OE1 D:GLU231 2.4 32.5 1.0 O D:ASN260 2.5 30.5 1.0 O D:GLU263 2.5 30.7 1.0 OD2 D:ASP273 2.5 26.2 1.0 OD2 D:ASP224 2.6 37.3 1.0 CD D:GLU231 3.2 32.5 1.0 OE2 D:GLU231 3.3 32.5 1.0 CG D:ASP224 3.5 37.3 1.0 CG D:ASP222 3.5 38.1 1.0 CG D:ASP273 3.6 26.2 1.0 C D:GLU263 3.6 30.7 1.0 C D:ASN260 3.7 30.5 1.0 OD1 D:ASP224 4.0 37.3 1.0 CB D:ASP273 4.1 26.2 1.0 CA D:SER264 4.1 29.7 1.0 CA D:TYR261 4.2 32.9 1.0 OD1 D:ASP222 4.2 38.1 1.0 N D:SER264 4.3 29.7 1.0 OG1 D:THR266 4.4 25.0 1.0 N D:TYR261 4.4 32.9 1.0 CA D:CA902 4.5 32.4 1.0 OG D:SER259 4.5 28.5 1.0 N D:GLU263 4.5 30.7 1.0 C D:SER264 4.5 29.7 1.0 CB D:ASP222 4.6 38.1 1.0 C D:TYR261 4.6 32.9 1.0 OD1 D:ASP273 4.6 26.2 1.0 CB D:ASP224 4.7 37.3 1.0 CG D:GLU231 4.7 32.5 1.0 O D:SER264 4.7 29.7 1.0 CA D:GLU263 4.7 30.7 1.0 CA D:ASN260 4.8 30.5 1.0 N D:ASN260 4.8 30.5 1.0 CB D:SER259 4.8 28.5 1.0 O D:TYR261 5.0 32.9 1.0

A.Kawamoto, T.Yamada, T.Yoshida, Y.Sato, T.Kato, H.Tsuge. Cryo-Em Structures of the Translocational Binary Toxin Complex Cdta-Bound Cdtb-Pore From Clostridioides Difficile. Nat Commun V. 13 6119 2022.
ISSN: ESSN 2041-1723
PubMed: 36253419
DOI: 10.1038/S41467-022-33888-4