7R4D image
Deposition Date 2022-02-08
Release Date 2023-02-08
Last Version Date 2023-02-08
Entry Detail
PDB ID:
7R4D
Keywords:
OXIDOREDUCTASE
Title:
Bovine complex I in the presence of IM1761092, deactive class vi (Composite map)
Biological Source:
Source Organism(s):
Bos taurus (Taxon ID: 9913)
Method Details:
Experimental Method:
ELECTRON MICROSCOPY
Resolution:
2.30 Å
Aggregation State:
PARTICLE
Reconstruction Method:
SINGLE PARTICLE
7R4D validation report
Macromolecular Entities
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH-ubiquinone oxidoreductas
Chain IDs:A
Chain Length:70
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P03898 Pfam ID:PF00507
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFS7
Chain IDs:B
Chain Length:84
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P42026 Pfam ID:PF01058
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFS3
Chain IDs:C
Chain Length:266
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P23709 Pfam ID:PF00329
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFS2
Mutagens:Q166R
Chain IDs:D
Chain Length:120
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P17694 Pfam ID:PF00346 EC:7.1.1.2
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFV2
Chain IDs:E
Chain Length:249
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P04394 Pfam ID:PF01257
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFV1
Chain IDs:F
Chain Length:57
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P25708 Pfam ID:PF01512, PF22461, PF10589
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH-ubiquinone oxidoreductas
Gene (Uniprot):NDUFS1
Chain IDs:G
Chain Length:727
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P15690 Pfam ID:PF00111, PF10588, PF22117, PF22151, PF00384, PF09326
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH-ubiquinone oxidoreductas
Gene (Uniprot):MT-ND1
Chain IDs:H
Chain Length:189
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P03887 Pfam ID:PF00146
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFS8
Chain IDs:I
Chain Length:212
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P42028 Pfam ID:PF12838
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH-ubiquinone oxidoreductas
Gene (Uniprot):MT-ND6
Chain IDs:J
Chain Length:108
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P03924 Pfam ID:PF00499
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH-ubiquinone oxidoreductas
Gene (Uniprot):MT-ND4L
Chain IDs:K
Chain Length:98
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P03902 Pfam ID:PF00420
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH-ubiquinone oxidoreductas
Gene (Uniprot):MT-ND5
Chain IDs:L
Chain Length:186
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P03920 Pfam ID:PF00662, PF00361, PF06455
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH-ubiquinone oxidoreductas
Gene (Uniprot):MT-ND4
Chain IDs:M
Chain Length:129
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P03910 Pfam ID:PF01059, PF00361
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH-ubiquinone oxidoreductas
Gene (Uniprot):MT-ND2
Chain IDs:N
Chain Length:179
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P03892 Pfam ID:PF00361, PF06444
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFA10
Mutagens:N278K
Chain IDs:O
Chain Length:137
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P34942 Pfam ID:PF01712
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFA9
Chain IDs:P
Chain Length:176
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P34943 Pfam ID:PF01370
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFS4
Chain IDs:Q
Chain Length:175
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02375 Pfam ID:PF04800
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFS6
Chain IDs:R
Chain Length:124
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P23934 Pfam ID:PF10276
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFA2
Chain IDs:S
Chain Length:99
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02370 Pfam ID:PF05047
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:Acyl carrier protein, mitocho
Gene (Uniprot):NDUFAB1
Chain IDs:T, U
Chain Length:156
Number of Molecules:2
Biological Source:Bos taurus
UniProt ID:P52505 Pfam ID:PF00550
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFA5
Chain IDs:V
Chain Length:116
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P23935 Pfam ID:PF04716
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFA6
Chain IDs:W
Chain Length:128
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02366 Pfam ID:PF13233
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFA8
Chain IDs:X
Chain Length:172
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P42029 Pfam ID:PF06747
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFA11
Chain IDs:Y
Chain Length:141
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q8HXG6 Pfam ID:PF02466
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFA13
Chain IDs:Z
Chain Length:144
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q95KV7 Pfam ID:PF06212
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFA1
Chain IDs:AA (auth: a)
Chain Length:70
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02377 Pfam ID:PF15879
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFA3
Chain IDs:BA (auth: b)
Chain Length:84
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02371 Pfam ID:PF14987
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFC1
Chain IDs:CA (auth: c)
Chain Length:266
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02376 Pfam ID:PF15088
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFC2
Chain IDs:DA (auth: d)
Chain Length:120
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02827 Pfam ID:PF06374
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFS5
Chain IDs:EA (auth: e)
Chain Length:249
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02379 Pfam ID:PF10200
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFB1
Chain IDs:FA (auth: f)
Chain Length:57
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02378 Pfam ID:PF08040
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFB11
Chain IDs:GA (auth: g)
Chain Length:727
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q8HXG5 Pfam ID:PF10183
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFB5
Chain IDs:HA (auth: h)
Chain Length:189
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02380 Pfam ID:PF09781
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFB6
Chain IDs:IA (auth: i)
Chain Length:212
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02367 Pfam ID:PF09782
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFB2
Chain IDs:JA (auth: j)
Chain Length:108
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02374 Pfam ID:PF14813
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFB3
Chain IDs:KA (auth: k)
Chain Length:98
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02365 Pfam ID:PF08122
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFB8
Chain IDs:LA (auth: l)
Chain Length:186
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02372 Pfam ID:PF05821
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFB4
Chain IDs:MA (auth: m)
Chain Length:129
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P48305 Pfam ID:PF07225
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFB9
Chain IDs:NA (auth: n)
Chain Length:179
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02369 Pfam ID:PF05347
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFB7
Chain IDs:OA (auth: o)
Chain Length:137
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02368 Pfam ID:PF05676
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFB10
Chain IDs:PA (auth: p)
Chain Length:176
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q02373 Pfam ID:PF10249
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFA12
Chain IDs:QA (auth: q)
Chain Length:175
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:O97725 Pfam ID:PF05071
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFA7
Chain IDs:RA (auth: r)
Chain Length:124
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:Q05752 Pfam ID:PF07347
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:NADH dehydrogenase [ubiquinon
Gene (Uniprot):NDUFV3
Chain IDs:SA (auth: s)
Chain Length:99
Number of Molecules:1
Biological Source:Bos taurus
UniProt ID:P25712 Pfam ID:PF15880
Modified Residue
Compound ID Chain ID Parent Comp ID Details 2D Image
2MR D ARG modified residue
AYA Y ALA modified residue
FME A MET modified residue
SAC IA SER modified residue
Ligand Molecules
3PE
CDL
EHZ
FES
FMN
GTP
I49
K
LMT
MG
MYR
NDP
PC1
SF4
ZN
Primary Citation
Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides.
Science 379 351 357 (2023)
PMID: 36701435 DOI: 10.1126/science.ade3332

Abstact

The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we define the inhibitory drug-target interaction(s) of a model biguanide with mammalian respiratory complex I by combining cryo-electron microscopy and enzyme kinetics. We interpret these data to explain the selectivity of biguanide binding to different enzyme states. The primary inhibitory site is in an amphipathic region of the quinone-binding channel, and an additional binding site is in a pocket on the intermembrane-space side of the enzyme. An independent local chaotropic interaction, not previously described for any drug, displaces a portion of a key helix in the membrane domain. Our data provide a structural basis for biguanide action and enable the rational design of medicinal biguanides.

Legend

Protein

Chemical

Disease

Primary Citation of related structures
7R4D
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