8WKZ: Melanocortin-4 Receptor

Crystal structure of the Melanocortin-4 Receptor (MC4R) in complex with S31. Determined by X-ray diffraction at 3.3 Å resolution. Released 7 Aug 2024.

Method: X-ray diffraction
Resolution: 3.3 Å
Organisms: Homo sapiens, synthetic construct
Chains: 2
Atoms: 3,769
Mol. weight: 62.84 kDa
Ligands: OLA, CA
Released: 7 Aug 2024

Explore 8WKZ in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8WKZ contains 23 α-helices and 6 β-strands across 1 chain. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 23 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	48-71	24
α-helix	73-75	3
α-helix	78-110	33
α-helix	118-152	35
α-helix	154-160	7
α-helix	163-186	24
α-helix	191-212	22
α-helix	213-217	5
α-helix	219-222	4
α-helix	1009-1011	3
α-helix	1016-1026	11
β-strand	1033-1038	6	1
α-helix	1048-1059	12
α-helix	1063-1066	4
β-strand	1067-1072	6	1
α-helix	1077-1088	12
β-strand	1093-1096	4	1
α-helix	1102-1109	8
β-strand	1114-1117	4	1
α-helix	1126-1133	8
β-strand	1137-1141	5	1
α-helix	1145-1149	5
β-strand	1156-1158	3	1
α-helix	1163-1176	14
α-helix	1182-1193	12
α-helix	239-270	32
α-helix	275-281	7
α-helix	284-304	21
α-helix	307-319	13

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Melanocortin receptor 4	A	protein	535	Homo sapiens	P32245 (AlphaFold model), Q9V2J8 (AlphaFold model)
[N-(3-{bis[2-(pyridin-2-yl-kappaN)ethyl]amino-kappaN}propyl)-5-(2-oxohexahydro-1H-thieno[3,4-d]imid…	B	protein	10	synthetic construct

Sequence of entity 1 (A), FASTA

>8WKZ_1 Melanocortin receptor 4 (chains A)
MKTIIALSYIFCLVFADYKDDDDAGRAWNRSSYRLHSNASESLGKGYSDGGCYEQLFVSP
VVFVTLGVISLLENILVIVAIAKNKNLHSPMYFFICSLAVADMLVSVSLGFETIVITLLN
STDTDAQSFTVNIDNVIDSVICASLLASICSLLSIAVDRYFTIFYALQYHNIMTVKRVGI
IISCIWAACTVSGILFIIYSDSSAVIICLITMFFTMLALMASLYVHMFLMARLHGIDCSF
WNESYLTGSRDERKKSLLSKFGMDEGVTFMFIGRFDRGQKGVDVLLKAIEILSSKKEFQE
MRFIIIGKGDPELEGWARSLEEKHGNVKVITEMLSREFVRELYGSVDFVIIPSYFEPFGL
VALEAMCLGAIPIASAVGGLRDIITNETGILVKAGDPGELANAILKALELSRSDLSKFRE
NCKKRAMSFSRQGANMKGAITLTILIGVFVVCWAPFFLHLIFYISCPQNPYCVCFMSHFN
LYLILIMCNSIINPLIYALRSQELRKTFKEIICCYEFLEVLFQGPHHHHHHHHHH

Sequence of entity 2 (B), FASTA

>8WKZ_2 [N-(3-{bis[2-(pyridin-2-yl-kappaN)ethyl]amino-kappaN}propyl)-5-(2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide](azido)(hydroxy)copper (chains B)
XLDPXRWRKX

Ligands and cofactors

ID	Name	Formula	Copies
OLA	Oleic acid	C18 H34 O2	5
CA	Calcium ion	Ca	1

Primary citation

Novel Cocrystal Structures of Peptide Antagonists Bound to the Human Melanocortin Receptor 4 Unveil Unexplored Grounds for Structure-Based Drug Design. Gimenez, L.E., Martin, C., Yu, J. et al. J Med Chem (2024) 67:2690-2711. DOI 10.1021/acs.jmedchem.3c01822 · PubMed

Other PDB entries of the same protein (UniProt P32245 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7PIU 2.58 Å, Cryo-EM structure of the agonist setmelanotide bound to the active melanocortin-4…
6W25 2.75 Å, Crystal structure of the Melanocortin-4 Receptor (MC4R) in complex with SHU9119
7PIV 2.86 Å, Active Melanocortin-4 receptor (MC4R)- Gs protein complex bound to agonist NDP-alpha-MSH…
8WKY 2.9 Å, Crystal structure of the Melanocortin-4 Receptor (MC4R) in complex with S25
7AUE 2.97 Å, Melanocortin receptor 4 (MC4R) Gs protein complex
7F53 3.0 Å, Cryo-EM structure of a-MSH-MC4R-Gs_Nb35 complex
7F54 3.0 Å, Cryo-EM structure of afamelanotide-MC4R-Gs_Nb35 complex
7F55 3.1 Å, Cryo-EM structure of bremelanotide-MC4R-Gs_Nb35 complex
7F58 3.1 Å, Cryo-EM structure of THIQ-MC4R-Gs_Nb35 complex
21LT 3.11 Å, Cryo-EM structure of the setmelanotide-bound human melanocortin receptor 4 (MC4R)-Gq…
9K3K 3.12 Å, Cryo-EM structure of the unliganded human melanocortin receptor 4 (MC4R)-Gs complex
8QJ2 3.4 Å, Structure of active state MC4R in complex with a potent ligand mimicking nanobody

Browse structure collections

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