6M0Z: Sodium-dependent dopamine transporter

X-ray structure of Drosophila dopamine transporter with NET-like mutations (D121G/S426M/F471L) in L-norepinephrine bound form. Determined by X-ray diffraction at 2.88 Å resolution. Released 17 Feb 2021.

Method: X-ray diffraction
Resolution: 2.88 Å
Organisms: Drosophila melanogaster, Mus musculus
Chains: 3
Atoms: 7,654
Mol. weight: 108.63 kDa
Ligands: CLR, DMU, LNR, Y01
Released: 17 Feb 2021

Explore 6M0Z in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6M0Z contains 57 α-helices and 49 β-strands across 3 chains. 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: 41 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	33-44	12
α-helix	48-51	4
α-helix	53-59	7
α-helix	62-65	4
α-helix	66-72	7
α-helix	73-77	5
α-helix	78-91	14
α-helix	95-102	8
α-helix	104-106	3
α-helix	108-137	30
α-helix	144-146	3
β-strand	158	1	1
β-strand	210	1	1
α-helix	211-214	4
α-helix	215-221	7
α-helix	223-225	3
β-strand	235	1	2
α-helix	237-251	15
α-helix	258-284	27
α-helix	289-297	9
α-helix	302-305	4
α-helix	307-321	15
α-helix	327-332	6
α-helix	341-373	33
α-helix	378-381	4
α-helix	386-387	2
α-helix	388-392	5
α-helix	393-397	5
α-helix	403-434	32
α-helix	438-442	5
α-helix	444-459	16
α-helix	460-462	3
β-strand	464	1	2
α-helix	467-477	11
α-helix	482-492	11
α-helix	493-499	7
α-helix	500-511	12
α-helix	514-516	3
α-helix	517-521	5
α-helix	522-526	5
α-helix	527-540	14
β-strand	546-547	2	3
β-strand	550-551	2	3
α-helix	554-568	15
α-helix	570-581	12
α-helix	586-592	7
α-helix	598-600	3

Chain H: 8 helices, 23 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	11-12	2	10
β-strand	18-25	8	9
α-helix	29-31	3
β-strand	34-39	6	11
β-strand	45-51	7	11
β-strand	58-60	3	11
β-strand	68-73	6	9
β-strand	78-83	6	9
α-helix	88-90	3
β-strand	92-98	7	11
β-strand	108-109	2	11
β-strand	113-115	3	11
β-strand	116-117	2	10
α-helix	120-122	3
β-strand	123	1	12
α-helix	124-125	2
β-strand	126-130	5	13
β-strand	141-151	11	13
β-strand	152	1	12
β-strand	157-160	4	14
α-helix	161-163	3
β-strand	165	1	14
β-strand	169-171	3	13
α-helix	172-174	3
β-strand	175-177	3	13
β-strand	180-190	11	13
α-helix	191-193	3
β-strand	200-205	6	14
α-helix	206-208	3
β-strand	210-215	6	14

Chain L: 8 helices, 20 β-strands

Element	Residues	Length	Sheet
β-strand	4-7	4	4
β-strand	10-13	4	5
β-strand	19-29	11	4
α-helix	31-33	3
β-strand	34-39	6	5
β-strand	46-50	5	5
β-strand	54-55	2	5
α-helix	56	1
β-strand	63-76	14	4
α-helix	81-83	3
β-strand	85-91	7	5
α-helix	97	1
β-strand	98-99	2	5
β-strand	103-107	5	5
β-strand	112	1	6
β-strand	115-119	5	7
α-helix	120-122	3
α-helix	123-128	6
β-strand	130-140	11	7
β-strand	141	1	6
β-strand	146-151	6	8
β-strand	154-156	3	8
β-strand	160-164	5	7
α-helix	165-168	4
β-strand	174-183	10	7
α-helix	184-188	5
β-strand	192-198	7	8
β-strand	206-211	6	8

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Sodium-dependent dopamine transporter	A	protein	536	Drosophila melanogaster	Q7K4Y6 (AlphaFold model)
Antibody fragment (Fab) 9D5 Light chain	L	protein	214	Mus musculus
Antibody fragment (Fab) 9D5 heavy chain	H	protein	219	Mus musculus

Sequence of entity 1 (A), FASTA

>6M0Z_1 Sodium-dependent dopamine transporter (chains A)
DERETWSGKVDFLLSVIGFAVDLANVWRFPYLCYKNGGGAFLVPYGIMLAVGGIPLFYME
LALGQHNRKGAITCWGRLVPLFKGIGYAVVLIAFYVGFYYNVIIAWSLRFFFASFTNSLP
WTSCNNIWNTPNCRPFEGHVEGFQSAASEYFNRYILELNRSEGIHDLGAIKWDMALCLLI
VYLICYFSLWKGISTSGKVVWFTALFPYAVLLILLIRGLTLPGSFLGIQYYLTPNFSAIY
KAEVWVDAATQVFFSLGPGFGVLLAYASYNKYHNNVYKDALLTSFINSATSFIAGFVIFS
VLGYMAHTLGVRIEDVATEGPGLVFVVYPAAIATMPASTFWALIFFMMLATLGLDSSFGG
MEAIITALSDEFPKIKRNRELFVAGLFSLYFVVGLASCTQGGFYFLHLLDRYAAGYSILV
AVFFEAIAVSWIYGTNRFSEDIRDMIGFPPGRYWQVCWRFVAPIFLLFITVYGLIGYEPL
TYADYVYPSWANALGWCIAGSSVVMIPAVAIFKLLSTPGSLRQRFTILTTPWRDQQ

Sequence of entity 2 (L), FASTA

>6M0Z_2 Antibody fragment (Fab) 9D5 Light chain (chains L)
ENVLTQSPAIMSTSPGEKVTMTCRASSSVGSSYLHWYQQKSGASPKLWIYSTSNLASGVP
ARFSGSGSGTSYSLTISSVEAEDAATYYCQQFSGYPLTFGSGTKLEMKRADAAPTVSIFP
PSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTL
TLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNE

Sequence of entity 3 (H), FASTA

>6M0Z_3 Antibody fragment (Fab) 9D5 heavy chain (chains H)
EVQLVESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQSPEKRLEWVAEISSGGRYIYY
SDTVTGRFTISRDNARNILHLEMSSLRSEDTAMYYCARGEVRQRGFDYWGQGTTLTVSSA
KTTAPSVYPLAPVCGDTTGSSVTLGCLVKGYFPEPVTLTWNSGSLSSGVHTFPAVLQSDL
YTLSSSVTVTSSTWPSQSITCNVAHPASSTKVDKKIEPR

Ligands and cofactors

ID	Name	Formula	Copies
CLR	Cholesterol	C27 H46 O	1
DMU	Decyl-beta-D-maltopyranoside	C22 H42 O11	1
LNR	L-norepinephrine	C8 H11 N O3	1
Y01	Cholesterol hemisuccinate	C31 H50 O4	1

Water and common crystallization additives (CL, NA) are not listed.

Primary citation

Structural basis of norepinephrine recognition and transport inhibition in neurotransmitter transporters. Pidathala, S., Mallela, A.K., Joseph, D. et al. Nat Commun (2021) 12:2199-2199. DOI 10.1038/s41467-021-22385-9 · PubMed

Other PDB entries of the same protein (UniProt Q7K4Y6 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7WGT 2.75 Å, X-ray structure of thermostabilized Drosophila dopamine transporter with GABA…
4XP4 2.8 Å, X-ray structure of Drosophila dopamine transporter in complex with cocaine
4XP9 2.8 Å, X-ray structure of Drosophila dopamine transporter bound to psychostimulant D-amphetamine
6M2R 2.8 Å, X-ray structure of a functional Drosophila dopamine transporter in L-norepinephrine…
4XP1 2.89 Å, X-ray structure of Drosophila dopamine transporter bound to neurotransmitter dopamine
4XPH 2.9 Å, X-ray structure of Drosophila dopamine transporter with subsiteB mutations (D121G/S426M)…
7WLW 2.9 Å, X-ray structure of thermostabilized Drosophila dopamine transporter with GABA…
4XPA 2.95 Å, X-ray structure of Drosophila dopamine transporter bound to 3,4dichlorophenethylamine
4M48 2.96 Å, X-ray structure of dopamine transporter elucidates antidepressant mechanism
4XNU 2.98 Å, X-ray structure of Drosophila dopamine transporter in complex with nisoxetine
4XNX 3.0 Å, X-ray structure of Drosophila dopamine transporter in complex with reboxetine
9EUP 3.0 Å, Inhibitor-free outward-open structure of Drosophila dopamine transporter

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