Structure of PDB 6ee3 Chain A Binding Site BS02

Receptor Information

>6ee3 Chain A (length=889) Species: 186763 (Plasmodium falciparum FcB1/Columbia)

PKIHYRKDYKPSGFIINQVTLNINIHDQETIVRSVLDMDISKHNVGEDLV
FDGVGLKINEISINNKKLVEGEEYTYDNEFLTIFSKFVPKSKFAFSSEVI
IHPETNYALTGLYKSKNIIVSQCEATGFRRITFFIDRPDMMAKYDVTVTA
DKEKYPVLLSNGDKVNEFEIPGGRHGARFNDPPLKPCYLFAVVAGDLKHL
SATYITKYTKKKVELYVFSEEKYVSKLQWALECLKKSMAFDEDYFGLEYD
LSRLNLVAVSDFNVGAMENKGLNIFNANSLLASKKNSIDFSYARILTVVG
HEYFHQYTGNRVTLRDWFQLTLKEGLTVHRENLFSEEMTKTVTTRLSHVD
LLRSVQFLEDSSPLSHPIRPESYVSMENFYTTTVYDKGSEVMRMYLTILG
EEYYKKGFDIYIKKNDGNTATCEDFNYAMEQAYKMKKADNSANLNQYLLW
FSQSGTPHVSFKYNYDAEKKQYSIHVNQYTKPDENQKEKKPLFIPISVGL
INPENGKEMISQTTLELTKESDTFVFNNIAVKPIPSLFRGFSAPVYIEDQ
LTDEERILLLKYDSDAFVRYNSCTNIYMKQILMNYNEFLKAKNEKLESFQ
LTPVNAQFIDAIKYLLEDPHADAGFKSYIVSLPQDRYIINFVSNLDTDVL
ADTKEYIYKQIGDKLNDVYYKMFKSLEAKADDLTYFNDESHVDFDQMNMR
TLRNTLLSLLSKAQYPNILNEIIEHSKSPYPSNWLTSLSVSAYFDKYFEL
YDKTYKLSKDDELLLQEWLKTVSRSDRKDIYEILKKLENEVLKDSKNPND
IRAVYLPFTNNLRRFHDISGKGYKLIAEVITKTDKFNPMVATQLCEPFKL
WNKLDTKRQELMLNEMNTMLQEPQISNNLKEYLLRLTNK

Ligand information

• Ligand ID: J4V
• InChI: InChI=1S/C25H25F3N2O3/c26-19-10-16(11-20(27)22(19)28)14-1-3-15(4-2-14)23(25(32)30-33)29-24(31)21-17-6-12-5-13(8-17)9-18(21)7-12/h1-4,10-13,17-18,21,23,33H,5-9H2,(H,29,31)(H,30,32)/t12-,13+,17-,18+,21-,23-/m1/s1
• InChIKey: CETVPXTYHVOGCT-YMWQUUDPSA-N
• SMILES:
  CACTVS 3.385: ONC(=O)[C@H](NC(=O)C1C2CC3CC(C2)CC1C3)c4ccc(cc4)c5cc(F)c(F)c(F)c5
  CACTVS 3.385: ONC(=O)[CH](NC(=O)C1C2CC3CC(C2)CC1C3)c4ccc(cc4)c5cc(F)c(F)c(F)c5
  ACDLabs 12.01: C1C3CC2CC(CC1C2)C3C(NC(c4ccc(cc4)c5cc(F)c(F)c(F)c5)C(=O)NO)=O
  OpenEye OEToolkits 2.0.6: c1cc(ccc1c2cc(c(c(c2)F)F)F)[C@H](C(=O)NO)NC(=O)C3C4CC5CC(C4)CC3C5
  OpenEye OEToolkits 2.0.6: c1cc(ccc1c2cc(c(c(c2)F)F)F)C(C(=O)NO)NC(=O)C3C4CC5CC(C4)CC3C5
• Formula: C25 H25 F3 N2 O3
• Name: (1R,2r,3S,5R,7R)-N-[(1R)-2-(hydroxyamino)-2-oxo-1-(3',4',5'-trifluoro[1,1'-biphenyl]-4-yl)ethyl]tricyclo[3.3.1.1~3,7~]decane-2-carboxamide
• PDB chain: 6ee3 Chain A Residue 1102

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6ee3 Hydroxamic Acid Inhibitors Provide Cross-Species Inhibition of Plasmodium M1 and M17 Aminopeptidases.
• Resolution: 1.82 Å
• Binding residue (original residue number in PDB): T305 Q317 E319 A320 V459 G460 A461 M462 E463 R489 H496 E497 H500 E519 E572 Y575 Y580 M1034
• Binding residue (residue number reindexed from 1): T110 Q122 E124 A125 V264 G265 A266 M267 E268 R294 H301 E302 H305 E324 E377 Y380 Y385 M839
• Annotation score: 1
• Binding affinity: MOAD: Ki=137nM
  PDBbind-CN: -logKd/Ki=6.86,Ki=137nM

Enzymatic activity

• Catalytic site (original residue number in PDB): E463 H496 E497 H500 E519 E572 Y580
• Catalytic site (residue number reindexed from 1): E268 H301 E302 H305 E324 E377 Y385
• 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:6ee3, PDBe:6ee3, PDBj:6ee3
• PDBsum: 6ee3
• PubMed: 30537832
• UniProt: O96935|AMPN_PLAF7 Aminopeptidase N (Gene Name=M1AAP)