Structure of PDB 4zx6 Chain A Binding Site BS02

Receptor Information

>4zx6 Chain A (length=888) Species: 186763 (Plasmodium falciparum FcB1/Columbia)

KIHYRKDYKPSGFIINQVTLNINIHDQETIVRSVLDMDISKHNVGEDLVF
DGVGLKINEISINNKKLVEGEEYTYDNEFLTIFSKFVPKSKFAFSSEVII
HPETNYALTGLYKSKNIIVSQCEATGFRRITFFIDRPDMMAKYDVTVTAD
KEKYPVLLSNGDKVNEFEIPGGRHGARFNDPPLKPCYLFAVVAGDLKHLS
ATYITKYTKKKVELYVFSEEKYVSKLQWALECLKKSMAFDEDYFGLEYDL
SRLNLVAVSDFNVGAMENKGLNIFNANSLLASKKNSIDFSYARILTVVGH
EYFHQYTGNRVTLRDWFQLTLKEGLTVHRENLFSEEMTKTVTTRLSHVDL
LRSVQFLEDSSPLSHPIRPESYVSMENFYTTTVYDKGSEVMRMYLTILGE
EYYKKGFDIYIKKNDGNTATCEDFNYAMEQAYKMKKADNSANLNQYLLWF
SQSGTPHVSFKYNYDAEKKQYSIHVNQYTKPDENQKEKKPLFIPISVGLI
NPENGKEMISQTTLELTKESDTFVFNNIAVKPIPSLFRGFSAPVYIEDQL
TDEERILLLKYDSDAFVRYNSCTNIYMKQILMNYNEFLKAKNEKLESFQL
TPVNAQFIDAIKYLLEDPHADAGFKSYIVSLPQDRYIINFVSNLDTDVLA
DTKEYIYKQIGDKLNDVYYKMFKSLEAKADDLTYFNDESHVDFDQMNMRT
LRNTLLSLLSKAQYPNILNEIIEHSKSPYPSNWLTSLSVSAYFDKYFELY
DKTYKLSKDDELLLQEWLKTVSRSDRKDIYEILKKLENEVLKDSKNPNDI
RAVYLPFTNNLRRFHDISGKGYKLIAEVITKTDKFNPMVATQLCEPFKLW
NKLDTKRQELMLNEMNTMLQEPQISNNLKEYLLRLTNK

Ligand information

• Ligand ID: 4U6
• InChI: InChI=1S/C20H24N4O4/c1-20(2,3)19(26)22-16(18(25)24-28)13-9-7-12(8-10-13)14-5-4-6-15(11-14)17(21)23-27/h4-11,16,27-28H,1-3H3,(H2,21,23)(H,22,26)(H,24,25)/t16-/m1/s1
• InChIKey: PJBKHMHOENYLFA-MRXNPFEDSA-N
• SMILES:
  CACTVS 3.385: CC(C)(C)C(=O)N[CH](C(=O)NO)c1ccc(cc1)c2cccc(c2)C(N)=NO
  OpenEye OEToolkits 1.9.2: CC(C)(C)C(=O)NC(c1ccc(cc1)c2cccc(c2)C(=NO)N)C(=O)NO
  ACDLabs 12.01: CC(C)(C)C(NC(C(=O)NO)c1ccc(cc1)c2cc(ccc2)/C(N)=N/O)=O
  OpenEye OEToolkits 1.9.2: CC(C)(C)C(=O)N[C@H](c1ccc(cc1)c2cccc(c2)/C(=N/O)/N)C(=O)NO
  CACTVS 3.385: CC(C)(C)C(=O)N[C@@H](C(=O)NO)c1ccc(cc1)c2cccc(c2)\C(N)=N\O
• Formula: C20 H24 N4 O4
• Name: N-{(1R)-2-(hydroxyamino)-1-[3'-(N'-hydroxycarbamimidoyl)biphenyl-4-yl]-2-oxoethyl}-2,2-dimethylpropanamide
• ZINC: ZINC000584905148
• PDB chain: 4zx6 Chain A Residue 1102

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4zx6 Potent dual inhibitors of Plasmodium falciparum M1 and M17 aminopeptidases through optimization of S1 pocket interactions.
• Resolution: 2.05 Å
• Binding residue (original residue number in PDB): V459 G460 A461 E463 H496 E497 H500 E519 E572 Y575 Y580 M1034
• Binding residue (residue number reindexed from 1): V263 G264 A265 E267 H300 E301 H304 E323 E376 Y379 Y384 M838
• Annotation score: 1
• Binding affinity: MOAD: Ki=5.4uM
  PDBbind-CN: -logKd/Ki=5.27,Ki=5.4uM

Enzymatic activity

• Catalytic site (original residue number in PDB): E463 H496 E497 H500 E519 E572 Y580
• Catalytic site (residue number reindexed from 1): E267 H300 E301 H304 E323 E376 Y384
• Enzyme Commision number: 3.4.11.-

Gene Ontology

Molecular Function

• GO:0008237 metallopeptidase activity
• GO:0008270 zinc ion binding

Biological Process

• GO:0006508 proteolysis

External links

• PDB: RCSB:4zx6, PDBe:4zx6, PDBj:4zx6
• PDBsum: 4zx6
• PubMed: 26807544
• UniProt: O96935|AMPN_PLAF7 Aminopeptidase N (Gene Name=M1AAP)