5HE5: BACE-1

BACE-1 in complex with (7aR)-7a-(5-cyanothiophen-2-yl)-6-(5-fluoro-4-methyl-6-(methylamino)pyrimidin-2-yl)-3-methyl-4-oxooctahydro-2H-pyrrolo[3,4-d]pyrimidin-2-iminium. Determined by X-ray diffraction at 1.55 Å resolution. Released 16 Mar 2016.

Method: X-ray diffraction
Resolution: 1.55 Å
Organism: Homo sapiens
Chains: 2
Atoms: 7,061
Mol. weight: 93.63 kDa
Ligands: 60S, TLA
Released: 16 Mar 2016

Explore 5HE5 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

5HE5 contains 26 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: 13 helices, 28 β-strands

Element	Residues	Length	Sheet
β-strand	67-70	4	1
β-strand	74-81	8	1
β-strand	86-93	8	1
β-strand	99-102	4	1
α-helix	115-117	3
β-strand	122-131	10	1
β-strand	136-147	12	1
β-strand	155-167	13	1
β-strand	178-181	4	1
α-helix	185-187	3
α-helix	197-204	8
β-strand	211-215	5	1
α-helix	224-229	6
β-strand	233-237	5	1
α-helix	242-244	3
β-strand	245-253	9	1
β-strand	257	1	2
β-strand	260	1	2
β-strand	261-262	2	3
β-strand	264-269	6	4
β-strand	272-273	2	4
α-helix	278-281	4
β-strand	286-288	3	3
β-strand	295-298	4	3
α-helix	299-312	14
α-helix	320-323	4
β-strand	329-331	3	5
α-helix	338-340	3
α-helix	342-343	2
β-strand	344-349	6	4
β-strand	355-361	7	4
α-helix	363-366	4
β-strand	367-370	4	5
β-strand	379-383	5	5
β-strand	385-388	4	3
β-strand	392-394	3	3
α-helix	396-399	4
β-strand	402-407	6	1
β-strand	412-418	7	1
β-strand	430-436	7	4
α-helix	440-443	4

Chain B: 13 helices, 28 β-strands

Element	Residues	Length	Sheet
β-strand	67-70	4	6
β-strand	74-81	8	6
β-strand	86-93	8	6
β-strand	99-102	4	6
α-helix	115-117	3
β-strand	122-131	10	6
β-strand	136-147	12	6
β-strand	155-167	13	6
β-strand	178-181	4	6
α-helix	185-187	3
α-helix	197-204	8
β-strand	211-215	5	6
α-helix	224-229	6
β-strand	233-237	5	6
α-helix	242-244	3
β-strand	245-253	9	6
β-strand	257	1	7
β-strand	260	1	7
β-strand	261-262	2	8
β-strand	264-269	6	9
β-strand	272-273	2	9
α-helix	278-282	5
β-strand	286-288	3	8
β-strand	295-298	4	8
α-helix	299-312	14
α-helix	320-323	4
β-strand	329-331	3	10
α-helix	338-340	3
α-helix	342-343	2
β-strand	344-349	6	9
β-strand	355-361	7	9
α-helix	363-366	4
β-strand	367-370	4	10
β-strand	379-383	5	10
β-strand	385-388	4	8
β-strand	392-394	3	8
α-helix	396-399	4
β-strand	402-407	6	6
β-strand	412-418	7	6
β-strand	430-436	7	9
α-helix	440-443	4

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Beta-secretase 1	A, B	protein	414	Homo sapiens	P56817 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>5HE5_1 Beta-secretase 1 (chains A, B)
LRLPRETDEEPEEPGRRGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFA
VGAAPHPFLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRANI
AAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPNLFSLQLCGAGF
PLNQSEVLASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEINGQDLKMDCKE
YNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPDGFWLGEQLVCWQAGTTPWNI
FPVISLYLMGEVTNQSFRITILPQQYLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIME
GFYVVFDRARKRIGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYNIPQTDEST

Ligands and cofactors

ID	Name	Formula	Copies
60S	5-{(2E,4aR,7aR)-6-[5-fluoro-4-methyl-6-(methylamino)pyrimidin-2-yl]-2-imino-3-m…	C18 H19 F N8 O S	2
TLA	L(+)-tartaric acid	C4 H6 O6	2

Primary citation

Structure-Based Design of an Iminoheterocyclic beta-Site Amyloid Precursor Protein Cleaving Enzyme (BACE) Inhibitor that Lowers Central A beta in Nonhuman Primates. Mandal, M., Wu, Y., Misiaszek, J. et al. J Med Chem (2016) 59:3231-3248. DOI 10.1021/acs.jmedchem.5b01995 · 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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