6BFE: Beta-secretase 1

BACE crystal structure with hydroxy pyrrolidine inhibitor. Determined by X-ray diffraction at 1.51 Å resolution. Released 15 Nov 2017.

Method: X-ray diffraction
Resolution: 1.51 Å
Organism: Homo sapiens
Chains: 2
Atoms: 7,232
Mol. weight: 99.22 kDa
Ligands: DJV
Released: 15 Nov 2017

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

Secondary structure: helices and β-sheets

6BFE contains 27 α-helices and 56 β-strands across 2 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: 14 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	-6--4	3
β-strand	6-9	4	1
β-strand	13-20	8	1
β-strand	25-32	8	1
β-strand	38-41	4	1
α-helix	54-56	3
β-strand	61-70	10	1
β-strand	75-86	12	1
β-strand	94-106	13	1
β-strand	117-120	4	1
α-helix	124-126	3
α-helix	136-143	8
β-strand	150-154	5	1
α-helix	163-168	6
β-strand	172-176	5	1
α-helix	181-183	3
β-strand	184-192	9	1
β-strand	196	1	2
β-strand	199	1	2
β-strand	200	1	3
β-strand	203-208	6	4
β-strand	211-212	2	4
α-helix	217-221	5
β-strand	225-227	3	3
β-strand	234-237	4	3
α-helix	238-251	14
α-helix	259-262	4
β-strand	268-270	3	5
α-helix	277-279	3
α-helix	281-282	2
β-strand	283-288	6	4
β-strand	294-300	7	4
α-helix	302-305	4
β-strand	306-309	4	5
β-strand	318-322	5	5
β-strand	324-327	4	3
β-strand	331-333	3	3
α-helix	335-338	4
β-strand	341-346	6	1
β-strand	351-357	7	1
β-strand	369-375	7	4
α-helix	379-382	4

Chain B: 13 helices, 28 β-strands

Element	Residues	Length	Sheet
β-strand	6-9	4	6
β-strand	13-20	8	6
β-strand	25-32	8	6
β-strand	38-41	4	6
α-helix	54-56	3
β-strand	61-70	10	6
β-strand	75-86	12	6
β-strand	94-106	13	6
β-strand	117-120	4	6
α-helix	124-126	3
α-helix	136-143	8
β-strand	150-154	5	6
α-helix	163-168	6
β-strand	172-176	5	6
α-helix	181-183	3
β-strand	184-192	9	6
β-strand	196	1	7
β-strand	199	1	7
β-strand	200	1	8
β-strand	203-208	6	9
β-strand	211-212	2	9
α-helix	217-221	5
β-strand	225-227	3	8
β-strand	234-237	4	8
α-helix	238-251	14
α-helix	259-262	4
β-strand	268-270	3	10
α-helix	277-279	3
α-helix	281-282	2
β-strand	283-288	6	9
β-strand	294-300	7	9
α-helix	302-305	4
β-strand	306-309	4	10
β-strand	318-322	5	10
β-strand	324-327	4	8
β-strand	331-333	3	8
α-helix	335-338	4
β-strand	341-346	6	6
β-strand	351-357	7	6
β-strand	369-375	7	9
α-helix	380-382	3

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Beta-secretase 1	A, B	protein	442	Homo sapiens	P56817 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>6BFE_1 Beta-secretase 1 (chains A, B)
MAGVLPAHGTQHGIRLPLRSGLGGAPLGLRLPRETDEEPEEPGRRGSFVEMVDNLRGKSG
QGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFLHRYYQRQLSSTYRDLRKGVYVPY
TQGKWEGELGTDLVSIPHGPNVTVRANIAAITESDKFFINGSNWEGILGLAYAEIARPDD
SLEPFFDSLVKQTHVPNLFSLQLCGAGFPLNQSEVLASVGGSMIIGGIDHSLYTGSLWYT
PIRREWYYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAA
SSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPVED
VATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHVHDEFRTAAVE
GPFVTLDMEDCGYNIPQTDEST

Ligands and cofactors

ID	Name	Formula	Copies
DJV	N-[(1R,2S)-1-[(2R,4R)-4-(cyclohexylmethoxy)pyrrolidin-2-yl]-3-(3,5-difluorophen…	C22 H32 F2 N2 O3	2

Water and common crystallization additives (GOL) are not listed.

Primary citation

Optimization of Hydroxyethylamine Transition State Isosteres as Aspartic Protease Inhibitors by Exploiting Conformational Preferences. Bueno, A.B., Agejas, J., Broughton, H. et al. J Med Chem (2017) 60:9807-9820. DOI 10.1021/acs.jmedchem.7b01304 · PubMed

Other PDB entries of the same protein (UniProt P56817 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7MYI 1.25 Å, BACE-1 in complex with compound #6
6UWP 1.29 Å, BACE-1 in complex with compound #32
6EQM 1.35 Å, Crystal Structure of Human BACE-1 in Complex with CNP520
4L7G 1.38 Å, Diethylaminosulfur Trifluoride-Mediated Intramolecular Cyclization of…
6EJ2 1.46 Å, BACE1 compound 28
6UWV 1.47 Å, BACE-1 in complex with compound #34
3VF3 1.48 Å, Crystal Structure of Human Beta Secretase in Complex with NVP-BQQ711
5HDZ 1.49 Å, BACE-1 in complex with (7aR)-7a-(5-cyanothiophen-2-yl)-6-(5-fluoro-4-methyl-6-(methylthio…
2QP8 1.5 Å, Structure of BACE Bound to SCH734723
4B78 1.5 Å, Aminoimidazoles as BACE-1 Inhibitors: From De Novo Design to Ab- lowering in Brain
4DJX 1.5 Å, Structure of BACE Bound to 5-(3-(5-chloropyridin-3-yl)phenyl)-5-cyclopropyl-2-imino-3-met…
5HU1 1.5 Å, BACE1 in complex with (R)-N-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thi…

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