Structure of PDB 1w6h Chain A Binding Site BS01

Receptor Information

>1w6h Chain A (length=325) Species: 5833 (Plasmodium falciparum)

SSNDNIELVDFQNIMFYGDAEVGDNQQPFTFILDTGSANLWVPSVKCTTA
GCLTKHLYDSSKSRTYEKDGTKVEMNYVSGTVSGFFSKDLVTVGNLSLPY
KFIEVIDTNGFEPTYTASTFDGILGLGWKDLSIGSVDPIVVELKNQNKIE
NALFTFYLPVHDKHTGFLTIGGIEERFYEGPLTYEKLNHDLYWQITLDAH
VGNIMLEKANCIVDSGTSAITVPTDFLNKMLQNLDVIKVFYVTLCNNSKL
PTFEFTSENGKYTLEPEYYLQHIEDVGPGLCMLNIIGLDFPVPTFILGDP
FMRKYFTVFDYDNHSVGIALAKKNL

Ligand information

• Ligand ID: TIT
• InChI: InChI=1S/C32H45BrN6O7/c1-18(2)14-24(29(34)42)37-30(43)20(5)36-27(41)15-26(40)25(17-46-16-21-9-11-22(33)12-10-21)38-32(45)28(19(3)4)39-31(44)23-8-6-7-13-35-23/h6-13,18-20,24-26,28,40H,14-17H2,1-5H3,(H2,34,42)(H,36,41)(H,37,43)(H,38,45)(H,39,44)/t20-,24-,25-,26-,28-/m0/s1
• InChIKey: QXHNYZQKWOKULQ-QPGFMSSHSA-N
• SMILES:
  ACDLabs 10.04: O=C(NC(C(=O)NC(C(O)CC(=O)NC(C(=O)NC(C(=O)N)CC(C)C)C)COCc1ccc(Br)cc1)C(C)C)c2ncccc2
  CACTVS 3.341: CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](COCc1ccc(Br)cc1)NC(=O)[C@@H](NC(=O)c2ccccn2)C(C)C)C(N)=O
  OpenEye OEToolkits 1.5.0: CC(C)CC(C(=O)N)NC(=O)C(C)NC(=O)CC(C(COCc1ccc(cc1)Br)NC(=O)C(C(C)C)NC(=O)c2ccccn2)O
  CACTVS 3.341: CC(C)C[CH](NC(=O)[CH](C)NC(=O)C[CH](O)[CH](COCc1ccc(Br)cc1)NC(=O)[CH](NC(=O)c2ccccn2)C(C)C)C(N)=O
  OpenEye OEToolkits 1.5.0: CC(C)C[C@@H](C(=O)N)NC(=O)[C@H](C)NC(=O)C[C@@H]([C@H](COCc1ccc(cc1)Br)NC(=O)[C@H](C(C)C)NC(=O)c2ccccn2)O
• Formula: C32 H45 Br N6 O7
• Name: N-((3S,4S)-5-[(4-BROMOBENZYL)OXY]-3-HYDROXY-4-{[N-(PYRIDIN-2-YLCARBONYL)-L-VALYL]AMINO}PENTANOYL)-L-ALANYL-L-LEUCINAMIDE
• ChEMBL: CHEMBL112598
• ZINC: ZINC000003925707
• PDB chain: 1w6h Chain A Residue 1330

Receptor-Ligand Complex Structure

Structure summary

• PDB: 1w6h Structural Study of a Novel Inhibitor with Bulky P1 Side Chain in Complex with Plasmepsin II -Implications for Drug Design
• Resolution: 2.24 Å
• Binding residue (original residue number in PDB): D34 N76 Y77 V78 S79 F111 T114 Y192 D214 G216 T217 S218
• Binding residue (residue number reindexed from 1): D34 N76 Y77 V78 S79 F111 T114 Y192 D214 G216 T217 S218
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=9.30,Ki=0.5nM
  BindingDB: Ki=2.2nM

Enzymatic activity

• Catalytic site (original residue number in PDB): D34 S37 N39 W41 Y77 D214 T217
• Catalytic site (residue number reindexed from 1): D34 S37 N39 W41 Y77 D214 T217
• Enzyme Commision number: 3.4.23.39: plasmepsin II.

Gene Ontology

Molecular Function

• GO:0004190 aspartic-type endopeptidase activity

Biological Process

• GO:0006508 proteolysis

External links

• PDB: RCSB:1w6h, PDBe:1w6h, PDBj:1w6h
• PDBsum: 1w6h
• UniProt: P46925|PLM2_PLAFX Plasmepsin II (Gene Name=PMII)