Structure of PDB 4jbs Chain B Binding Site BS02

Receptor Information

>4jbs Chain B (length=854) Species: 9606 (Homo sapiens)

VATNGERFPWQELRLPSVVIPLHYDLFVHPNLTSLDFVASEKIEVLVSNA
TQFIILHSKDLEITNATLQSEPGKELKVLSYPAHEQIALLVPEKLTPHLK
YYVAMDFQAKLGDGFEGFYKSTYRTLGGETRILAVTDFEPTQARMAFPCF
DEPLFKANFSIKIRRESRHIALSNMPKVKTIELEGGLLEDHFETTVKMST
YLVAYIVCDFHSLSGFTSSGVKVSIYASPDKRNQTHYALQASLKLLDFYE
KYFDIYYPLSKLDLIAIPDFAPGAMENWGLITYRETSLLFDPKTSSASDK
LWVTRVIAHELAHQWFGNLVTMEWWNDIWLKEGFAKYMELIAVNATYPEL
QFDDYFLNVCFEVITKDSLNSSRPISKPAETPTQIQEMFDEVSYNKGACI
LNMLKDFLGEEKFQKGIIQYLKKFSYRNAKNDDLWSSLSNSAEVKEMMTT
WTLQKGIPLLDGCSLRLQQERFLQGVERYLWHIPLTTSSSNVIHRHILKS
KTDTLDLPEKTSWVKFNVDSNGYYIVHYEGHGWDQLITQLNQNHTLLRPK
DRVGLIHDVFQLVGAGRLTLDKALDMTYYLQHETSSPALLEGLSYLESFY
HMMDRRNISDISENLKRYLLQYFKPVIDRQSWSDKGSVWDRMLRSALLKL
ACDLNHAPCIQKAAELFSQWMESSGKLNIPTDVLKIVYSVGAQTTAGWNY
LLEQYELSMSSAEQNKILYALSTSKHQEKLLKLIELGMEGKVIKTQNLAA
LLHAIARRPKGQQLAWDFVRENWTHLLKKFDLGSYDIRMIISGTTAHFSS
KDKLQEVKLFFESLEAQGSHLDIFQTVLETITKNIKWLEKNLPTLRTWLM
VNTR

Ligand information

• Ligand ID: P52
• InChI: InChI=1S/C27H37N4O4P/c1-18(2)14-21(17-36(34,35)25(28)13-12-19-8-4-3-5-9-19)27(33)31-24(26(29)32)15-20-16-30-23-11-7-6-10-22(20)23/h3-11,16,18,21,24-25,30H,12-15,17,28H2,1-2H3,(H2,29,32)(H,31,33)(H,34,35)/t21-,24+,25-/m1/s1
• InChIKey: QKFOTLXPIIESQI-IEZKXTBUSA-N
• SMILES:
  OpenEye OEToolkits 1.7.6: CC(C)C[C@H](CP(=O)([C@H](CCc1ccccc1)N)O)C(=O)N[C@@H](Cc2c[nH]c3c2cccc3)C(=O)N
  ACDLabs 12.01: O=P(O)(C(N)CCc1ccccc1)CC(C(=O)NC(C(=O)N)Cc3c2ccccc2nc3)CC(C)C
  OpenEye OEToolkits 1.7.6: CC(C)CC(CP(=O)(C(CCc1ccccc1)N)O)C(=O)NC(Cc2c[nH]c3c2cccc3)C(=O)N
  CACTVS 3.370: CC(C)C[C@H](C[P](O)(=O)[C@@H](N)CCc1ccccc1)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(N)=O
  CACTVS 3.370: CC(C)C[CH](C[P](O)(=O)[CH](N)CCc1ccccc1)C(=O)N[CH](Cc2c[nH]c3ccccc23)C(N)=O
• Formula: C27 H37 N4 O4 P
• Name: Nalpha-[(2S)-2-{[[(1R)-1-amino-3-phenylpropyl](hydroxy)phosphoryl]methyl}-4-methylpentanoyl]-L-tryptophanamide
• ChEMBL: CHEMBL3416733
• ZINC: ZINC000098209288
• PDB chain: 4jbs Chain B Residue 1010

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4jbs Rationally designed inhibitor targeting antigen-trimming aminopeptidases enhances antigen presentation and cytotoxic T-cell responses.
• Resolution: 2.789 Å
• Binding residue (original residue number in PDB): E200 A335 M336 H370 E371 E393 F450 Y455 Y892
• Binding residue (residue number reindexed from 1): E139 A274 M275 H309 E310 E332 F389 Y394 Y785
• Annotation score: 1
• Binding affinity: BindingDB: IC50=11nM

Enzymatic activity

• Catalytic site (original residue number in PDB): E337 H370 E371 H374 E393 Q447 Y455
• Catalytic site (residue number reindexed from 1): E276 H309 E310 H313 E332 Q386 Y394
• Enzyme Commision number: 3.4.11.-

Gene Ontology

Molecular Function

• GO:0004175 endopeptidase activity
• GO:0004177 aminopeptidase activity
• GO:0005515 protein binding
• GO:0008237 metallopeptidase activity
• GO:0008270 zinc ion binding
• GO:0042277 peptide binding
• GO:0046872 metal ion binding
• GO:0070006 metalloaminopeptidase activity

Biological Process

• GO:0002250 adaptive immune response
• GO:0002474 antigen processing and presentation of peptide antigen via MHC class I
• GO:0006508 proteolysis
• GO:0008217 regulation of blood pressure
• GO:0019885 antigen processing and presentation of endogenous peptide antigen via MHC class I
• GO:0043171 peptide catabolic process

Cellular Component

• GO:0005615 extracellular space
• GO:0005737 cytoplasm
• GO:0005783 endoplasmic reticulum
• GO:0005788 endoplasmic reticulum lumen
• GO:0005789 endoplasmic reticulum membrane
• GO:0016020 membrane

External links

• PDB: RCSB:4jbs, PDBe:4jbs, PDBj:4jbs
• PDBsum: 4jbs
• PubMed: 24248368
• UniProt: Q6P179|ERAP2_HUMAN Endoplasmic reticulum aminopeptidase 2 (Gene Name=ERAP2)