Structure of PDB 7pfs Chain A Binding Site BS01

Receptor Information

>7pfs Chain A (length=916) Species: 9606 (Homo sapiens)

EDPGAFPVATNGERFPWQELRLPSVVIPLHYDLFVHPNLTSLDFVASEKI
EVLVSNATQFIILHSKDLEITNATLQSEEDSRYMKPGKELKVLSYPAHEQ
IALLVPEKLTPHLKYYVAMDFQAKLGDGFEGFYKSTYRTLGGETRILAVT
DFEPTQARMAFPCFDEPLFKANFSIKIRRESRHIALSNMPKVKTIELEGG
LLEDHFETTVKMSTYLVAYIVCDFHSLSGFTSSGVKVSIYASPDKRNQTH
YALQASLKLLDFYEKYFDIYYPLSKLDLIAIPDFAPGAMENWGLITYRET
SLLFDPKTSSASDKLWVTRVIAHELAHQWFGNLVTMEWWNDIWLNEGFAK
YMELIAVNATYPELQFDDYFLNVCFEVITKDSLNSSRPISKPAETPTQIQ
EMFDEVSYNKGACILNMLKDFLGEEKFQKGIIQYLKKFSYRNAKNDDLWS
SLSNSCLESDFTSGGVCHSDPKMTSNMLAFLGENAEVKEMMTTWTLQKGI
PLLVVKQDGCSLRLQQERFLQGVFQEDPEWRALQERYLWHIPLTYSTSSS
NVIHRHILKSKTDTLDLPEKTSWVKFNVDSNGYYIVHYEGHGWDQLITQL
NQNHTLLRPKDRVGLIHDVFQLVGAGRLTLDKALDMTYYLQHETSSPALL
EGLSYLESFYHMMDRRNISDISENLKRYLLQYFKPVIDRQSWSDKGSVWD
RMLRSALLKLACDLNHAPCIQKAAELFSQWMESSGKLNIPTDVLKIVYSV
GAQTTAGWNYLLEQYELSMSSAEQNKILYALSTSKHQEKLLKLIELGMEG
KVIKTQNLAALLHAIARRPKGQQLAWDFVRENWTHLLKKFDLGSYDIRMI
ISGTTAHFSSKDKLQEVKLFFESLEAQGSHLDIFQTVLETITKNIKWLEK
NLPTLRTWLMVNTRHH

Ligand information

• Ligand ID: 7OO
• InChI: InChI=1S/C37H44N3O4P/c1-26(2)20-34(36(39)41)40-37(42)33(25-45(43,44)35(38)19-18-27-12-6-3-7-13-27)23-28-21-31(29-14-8-4-9-15-29)24-32(22-28)30-16-10-5-11-17-30/h3-17,21-22,24,26,33-35H,18-20,23,25,38H2,1-2H3,(H2,39,41)(H,40,42)(H,43,44)/t33-,34+,35-/m1/s1
• InChIKey: RAXDQSLZABPHNA-GVBYMILNSA-N
• SMILES:
  OpenEye OEToolkits 2.0.7: CC(C)CC(C(=O)N)NC(=O)C(Cc1cc(cc(c1)c2ccccc2)c3ccccc3)CP(=O)(C(CCc4ccccc4)N)O
  CACTVS 3.385: CC(C)C[C@H](NC(=O)[C@H](Cc1cc(cc(c1)c2ccccc2)c3ccccc3)C[P](O)(=O)[C@@H](N)CCc4ccccc4)C(N)=O
  CACTVS 3.385: CC(C)C[CH](NC(=O)[CH](Cc1cc(cc(c1)c2ccccc2)c3ccccc3)C[P](O)(=O)[CH](N)CCc4ccccc4)C(N)=O
  OpenEye OEToolkits 2.0.7: CC(C)C[C@@H](C(=O)N)NC(=O)[C@H](Cc1cc(cc(c1)c2ccccc2)c3ccccc3)CP(=O)([C@H](CCc4ccccc4)N)O
• Formula: C37 H44 N3 O4 P
• Name: [(2~{S})-3-[[(2~{S})-1-azanyl-4-methyl-1-oxidanylidene-pentan-2-yl]amino]-2-[(3,5-diphenylphenyl)methyl]-3-oxidanylidene-propyl]-[(1~{R})-1-azanyl-3-phenyl-propyl]phosphinic acid
• ChEMBL: CHEMBL4086352
• PDB chain: 7pfs Chain A Residue 1006

Receptor-Ligand Complex Structure

Structure summary

• PDB: 7pfs Inhibitor-Dependent Usage of the S1' Specificity Pocket of ER Aminopeptidase 2.
• Resolution: 2.7 Å
• Binding residue (original residue number in PDB): E200 P333 A335 E337 R345 W363 H370 E371 H374 E393 F450 Y455 Y892
• Binding residue (residue number reindexed from 1): E153 P286 A288 E290 R298 W316 H323 E324 H327 E346 F403 Y408 Y845
• Annotation score: 1

Enzymatic activity

• 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:7pfs, PDBe:7pfs, PDBj:7pfs
• PDBsum: 7pfs
• PubMed: 35178178
• UniProt: Q6P179|ERAP2_HUMAN Endoplasmic reticulum aminopeptidase 2 (Gene Name=ERAP2)