MolNFT v1 · #112326 · protein

Novel binding site for allosteric activation of ampk

4ZHX · 5'-AMP-activated protein kinase catalytic subunit alpha-2: “Novel binding site for allosteric activation of ampk”. X-ray diffraction, 4 ligands (4O7, C1V, C2Z), 20 pockets (best druggability 0.80). MolNFT v1 #112326 on GenesisL1: 3D…

PDB: 4ZHX
Type: protein
Length: 1,807 residues
Chains: 6
Method: x-ray diffraction
Collection: MolNFT v1 / PDB
Contract: 0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
Owner: 0x3396CDB397284571d12822B4ae1189a8E22AAAAA
Molecule: 5'-AMP-activated protein kinase catalytic subunit alpha-2; 5'-AMP-activated protein…
EC: 2.7.11.1, 2.7.11.27, 2.7.11.31
UniProt: P54646, Q9Y478, P54619
Ligands: 4O7, C1V, C2Z, AMP
Pockets: 20 · best druggability 0.80

Structure

x-ray diffraction · 6 distinct chains · 32% helix, 25% strand (DSSP).

Chain	Molecule	Type	Residues	Secondary structure	UniProt
A	5'-AMP-activated protein kinase catalytic subunit alpha-2 (EC 2.7.11.1, 2.7.11.27, 2.7.11.31)	protein	409	36% helix, 22% strand	P54646
B	5'-AMP-activated protein kinase subunit beta-1	protein	172	10% helix, 38% strand	Q9Y478
C	5'-AMP-activated protein kinase catalytic subunit alpha-2 (EC 2.7.11.1, 2.7.11.27, 2.7.11.31)	protein	453	36% helix, 20% strand	P54646
D	5'-AMP-activated protein kinase subunit beta-1	protein	175	11% helix, 39% strand	Q9Y478
E	5'-AMP-activated protein kinase subunit gamma-1	protein	298	39% helix, 23% strand	P54619
F	5'-AMP-activated protein kinase subunit gamma-1	protein	300	40% helix, 22% strand	P54619

Ligands and binding sites

4O7 · (5s,6r,7r,9r,13cr,14r,16as)-6-methoxy-5-methyl-7-(methylamino)-6,7,8,9,14,15,16,16A-octahydro-5h,13ch-5,9-epoxy-4B,9A,1 5-triazadibenzo[b,h]cyclonona[1,2,3, 4-jkl]cyclopenta[e]-as-indacen-14-ol · ligand · 2 copies · chains A, C
C1V · 3-[4-(2-hydroxyphenyl)phenyl]-4-oxidanyl-6-oxidanylidene-7H-thieno[2,3-b]pyridine-5-carbonitrile · ligand · 2 copies · chains A, B, C, D
C2Z · 5-(5-hydroxyl-isoxazol-3-yl)-furan-2-phosphonic acid · ligand · 2 copies · chains E
AMP · Adenosine monophosphate · ligand · 2 copies · chains C, F

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

Pockets

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

Pocket	Volume (Å³)	Druggability	Buriedness	Lining residues	Inside
1	1165	0.80	0.81	100	C2Z
2	851	0.80	0.83	82	AMP
3	1013	0.77	0.79	67	empty
4	998	0.75	0.78	67	empty
5	352	0.72	0.84	34	AMP

Interfaces

7 interfaces between chains.

C–D · 4144 Å² buried · 50 hydrogen bonds · protein-protein
A–B · 3538 Å² buried · 40 hydrogen bonds · protein-protein
C–F · 1646 Å² buried · 23 hydrogen bonds · protein-protein
D–F · 1280 Å² buried · 19 hydrogen bonds · protein-protein
B–E · 1268 Å² buried · 22 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 4 modified (phosphorylation).

Compared structures

4ZHX · Novel binding site for allosteric activation of AMPK · the same entry in another collection · chain F against F, TM-score 1.00
P54619 · AlphaFold monomer V2.0 prediction for 5'-AMP-activated protein kinase subunit gamma-1… · a predicted model of the same protein · chain F against A, TM-score 0.97
P54646 · AlphaFold monomer V2.0 prediction for 5'-AMP-activated protein kinase catalytic subunit… · a predicted model of the same protein · chain A against A, TM-score 0.95
Q9Y478 · AlphaFold monomer V2.0 prediction for 5'-AMP-activated protein kinase subunit beta-1… · a predicted model of the same protein · chain B against A, TM-score 0.88

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 P54646
Every structure of UniProt Q9Y478
Every structure of UniProt P54619
Elsewhere: RCSB PDB 4ZHX · PDBe 4ZHX · UniProt P54646 · UniProt Q9Y478 · UniProt P54619

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