Structure of PDB 2qmg Chain B Binding Site BS01

Receptor Information

>2qmg Chain B (length=389) Species: 9606 (Homo sapiens)

GSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHP
FLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVR
ANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHV
PNLFSLQLCGAGFPLNQSEVLASVGGSMIIGGIDHSLYTGSLWYTPIRRE
WYYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVK
SIKAASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSF
RITILPQQYLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFD
RARKRIGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYN

Ligand information

• Ligand ID: SC6
• InChI: InChI=1S/C34H39F2N3O5/c1-21-11-23(16-24(12-21)34(42)39-10-6-7-27(39)20-43-2)33(41)38-31(15-22-13-25(35)17-26(36)14-22)32(40)30-18-29(19-37-30)44-28-8-4-3-5-9-28/h3-5,8-9,11-14,16-17,27,29-32,37,40H,6-7,10,15,18-20H2,1-2H3,(H,38,41)/t27-,29-,30-,31+,32-/m1/s1
• InChIKey: KYHYNSQLYDXSNK-MXWGZHRFSA-N
• SMILES:
  CACTVS 3.341: COC[CH]1CCCN1C(=O)c2cc(C)cc(c2)C(=O)N[CH](Cc3cc(F)cc(F)c3)[CH](O)[CH]4C[CH](CN4)Oc5ccccc5
  CACTVS 3.341: COC[C@H]1CCCN1C(=O)c2cc(C)cc(c2)C(=O)N[C@@H](Cc3cc(F)cc(F)c3)[C@H](O)[C@H]4C[C@H](CN4)Oc5ccccc5
  ACDLabs 10.04: O=C(N1CCCC1COC)c2cc(cc(c2)C)C(=O)NC(Cc3cc(F)cc(F)c3)C(O)C5NCC(Oc4ccccc4)C5
  OpenEye OEToolkits 1.5.0: Cc1cc(cc(c1)C(=O)N2CCCC2COC)C(=O)NC(Cc3cc(cc(c3)F)F)C(C4CC(CN4)Oc5ccccc5)O
  OpenEye OEToolkits 1.5.0: Cc1cc(cc(c1)C(=O)N2CCC[C@@H]2COC)C(=O)N[C@@H](Cc3cc(cc(c3)F)F)[C@@H]([C@H]4C[C@H](CN4)Oc5ccccc5)O
• Formula: C34 H39 F2 N3 O5
• Name: N-{(1S,2R)-1-(3,5-DIFLUOROBENZYL)-2-HYDROXY-2-[(2R,4R)-4-PHENOXYPYRROLIDIN-2-YL]ETHYL}-3-{[(2R)-2-(METHOXYMETHYL)PYRROLIDIN-1-YL]CARBONYL}-5-METHYLBENZAMIDE
• ChEMBL: CHEMBL403195
• ZINC: ZINC000014209296
• PDB chain: 2qmg Chain B Residue 1

Receptor-Ligand Complex Structure

Structure summary

• PDB: 2qmg Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor.
• Resolution: 1.89 Å
• Binding residue (original residue number in PDB): G72 D93 G95 S96 Y132 T133 Q134 F169 R189 D289 G291 T292 T293 R296
• Binding residue (residue number reindexed from 1): G15 D36 G38 S39 Y75 T76 Q77 F112 R132 D232 G234 T235 T236 R239
• Annotation score: 1
• Binding affinity: MOAD: Ki=0.7nM

Enzymatic activity

• Catalytic site (original residue number in PDB): D93 S96 N98 A100 Y132 D289 T292
• Catalytic site (residue number reindexed from 1): D36 S39 N41 A43 Y75 D232 T235
• Enzyme Commision number: 3.4.23.46: memapsin 2.

Gene Ontology

Molecular Function

• GO:0004190 aspartic-type endopeptidase activity

Biological Process

• GO:0006508 proteolysis

Cellular Component

• GO:0016020 membrane

External links

• PDB: RCSB:2qmg, PDBe:2qmg, PDBj:2qmg
• PDBsum: 2qmg
• PubMed: 17980584
• UniProt: P56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)