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Binding site elucidation and structure guided design of macrocyclic il-17A antagonists

Analyse Binding site elucidation and structure guided design of macrocyclic il-17A… in the GL1X research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides, crosslinks and neighbours on the 3D structure.

PDB: 5HI3
Type: protein
Length: 1,068 residues
Chains: 7
Method: x-ray diffraction
Collection: MolNFT v1 / PDB
Contract: 0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
Owner: 0x3396CDB397284571d12822B4ae1189a8E22AAAAA
Molecule: Interleukin-17A; Cat-2000 Fab heavy chain; Cat-2000 Fab light chain; Synthetic il-17A…
UniProt: Q16552
Ligands: 63O
Pockets: 14 · best druggability 0.76

Structure

x-ray diffraction · 5 distinct chains · 8% helix, 52% strand (DSSP).

Chain	Molecule	Type	Residues	Secondary structure	UniProt
A	Interleukin-17A	protein	100	4% helix, 53% strand	Q16552
B	Interleukin-17A	protein	88	5% helix, 57% strand	Q16552
C, H	Cat-2000 Fab heavy chain	protein	220	10% helix, 53% strand	—
D, L	Cat-2000 Fab light chain	protein	213	8% helix, 50% strand	—
I	Synthetic il-17A peptide inhibitor	protein	14	50% helix, 36% strand	—

Ligands and binding sites

63O · N-(4-{2-[({1-[2-(dimethylamino)-2-oxoethyl]cyclopentyl}acetyl)amino]ethyl}phenyl)-2-fluoro-Nalpha-[(1-methyl-1H-pyrazol-5-yl)carbonyl]-L-phenylalaninamide · ligand · chains A, B

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

14 pockets found on a 1 Å grid, 6 with a druggability of 0.5 or more.

Pocket	Volume (Å³)	Druggability	Buriedness	Lining residues	Inside
1	1153	0.76	0.78	95	63O
2	266	0.66	0.82	47	empty
3	451	0.58	0.74	61	empty
4	138	0.55	0.82	35	empty
5	347	0.54	0.74	38	empty

Interfaces

11 interfaces between chains.

H–L · 1847 Å² buried · 19 hydrogen bonds · protein-protein
C–D · 1802 Å² buried · 19 hydrogen bonds · protein-protein
A–B · 1174 Å² buried · 13 hydrogen bonds · protein-protein
A–I · 669 Å² buried · 12 hydrogen bonds · protein-protein
A–D · 363 Å² buried · 3 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 12 disulfide (disulfide).

Compared structures

5HI3 · Binding site elucidation and structure guided design of macrocyclic IL-17A antagonists · the same entry in another collection · chain L against L, TM-score 1.00
Q16552 · AlphaFold monomer V2.0 prediction for interleukin-17A (Q16552) · a predicted model of the same protein · chain B against A, TM-score 0.87

Analyse

Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
Every structure of UniProt Q16552
Elsewhere: RCSB PDB 5HI3 · PDBe 5HI3 · UniProt Q16552

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