Structure of PDB 4hzt Chain A

Receptor sequence

>4hztA (length=393) Species: 9606 (Homo sapiens)

GSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHP
FLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVR
ANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHV
PNLFSLQLCGLASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRV
EINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEK
FPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYL
RPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAV
SACHVHDEFRTAAVEGPFVTLDMEDCGYNIPQTDESRSHHHHH

3D structure

• PDB: 4hzt Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates.
• Chain: A
• Resolution: 1.8 Å

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 D222 T225
• Enzyme Commision number: 3.4.23.46: memapsin 2.

Interaction with ligand

Site #	Ligand	Ligand chain	Binding residues on receptor (original residue number in PDB)	Binding residues on receptor (residue number reindexed from 1)	Binding affinity
BS01	ZN	A	H457 H459	H390 H392
BS02	ZN	A	D192 H458 H460	D135 H391 H393
BS03	ZN	A	E78 H150	E21 H93
BS04	0ZA	A	Q73 G74 L91 D93 Y132 Q134 G135 F169 W176 G291 T292 T293 N294	Q16 G17 L34 D36 Y75 Q77 G78 F112 W119 G224 T225 T226 N227	MOAD: ic50=0.75uM PDBbind-CN: -logKd/Ki=6.12,IC50=0.75uM

Gene Ontology

Molecular Function

• GO:0004190 aspartic-type endopeptidase activity

Biological Process

• GO:0006508 proteolysis

Cellular Component

• GO:0016020 membrane

External links

• PDB: RCSB:4hzt, PDBe:4hzt, PDBj:4hzt
• PDBsum: 4hzt
• PubMed: 23465612
• UniProt: P56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)