Structure of PDB 5k1v Chain A Binding Site BS02

Receptor Information

>5k1v Chain A (length=899) Species: 9606 (Homo sapiens)

PVATNGERFPWQELRLPSVVIPLHYDLFVHPNLTSLDFVASEKIEVLVSN
ATQFIILHSKDLEITNATLQSEEDSRYMKPGKELKVLSYPAHEQIALLVP
EKLTPHLKYYVAMDFQAKLGDGFEGFYKSTYRTLGGETRILAVTDFEPTQ
ARMAFPCFDEPLFKANFSIKIRRESRHIALSNMPKVKTIELEGGLLEDHF
ETTVKMSTYLVAYIVCDFHSLSGFTSSGVKVSIYASPDKRNQTHYALQAS
LKLLDFYEKYFDIYYPLSKLDLIAIPDFAPGAMENWGLITYRETSLLFDP
KTSSASDKLWVTRVIAHELAHQWFGNLVTMEWWNDIWLKEGFAKYMELIA
VNATYPELQFDDYFLNVCFEVITKDSLNSSRPISKPAETPTQIQEMFDEV
SYNKGACILNMLKDFLGEEKFQKGIIQYLKKFSYRNAKNDDLWSSLSNSC
GVCHSMTSNMLAFLGENAEVKEMMTTWTLQKGIPLLVVKQDGCSLRLQQE
RFLQGVFQEDPEWRALQERYLWHIPLTYSTSSSNVIHRHILKSKTDTLDL
PEKTSWVKFNVDSNGYYIVHYEGHGWDQLITQLNQNHTLLRPKDRVGLIH
DVFQLVGAGRLTLDKALDMTYYLQHETSSPALLEGLSYLESFYHMMDRRN
ISDISENLKRYLLQYFKPVIDRQSWSDKGSVWDRMLRSALLKLACDLNHA
PCIQKAAELFSQWMESSGKLNIPTDVLKIVYSVGAQTTAGWNYLLEQYEL
SMSSAEQNKILYALSTSKHQEKLLKLIELGMEGKVIKTQNLAALLHAIAR
RPKGQQLAWDFVRENWTHLLKKFDLGSYDIRMIISGTTAHFSSKDKLQEV
KLFFESLEAQGSHLDIFQTVLETITKNIKWLEKNLPTLRTWLMVNTRHH

Ligand information

• Ligand ID: 6PX
• InChI: InChI=1S/C23H31N7O5/c1-35-22(34)19(11-13-4-7-15(31)8-5-13)30-20(32)14-6-9-16(24)18(12-14)29-21(33)17(25)3-2-10-28-23(26)27/h4-9,12,17,19,31H,2-3,10-11,24-25H2,1H3,(H,29,33)(H,30,32)(H4,26,27,28)/t17-,19-/m0/s1
• InChIKey: JECKMXQKZJERLG-HKUYNNGSSA-N
• SMILES:
  CACTVS 3.385: COC(=O)[CH](Cc1ccc(O)cc1)NC(=O)c2ccc(N)c(NC(=O)[CH](N)CCCNC(N)=N)c2
  CACTVS 3.385: COC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)c2ccc(N)c(NC(=O)[C@@H](N)CCCNC(N)=N)c2
  OpenEye OEToolkits 2.0.4: [H]/N=C(/N)\NCCC[C@@H](C(=O)Nc1cc(ccc1N)C(=O)N[C@@H](Cc2ccc(cc2)O)C(=O)OC)N
  ACDLabs 12.01: C(CCCNC(\N)=N)(C(Nc1c(N)ccc(c1)C(NC(C(=O)OC)Cc2ccc(cc2)O)=O)=O)N
  OpenEye OEToolkits 2.0.4: COC(=O)C(Cc1ccc(cc1)O)NC(=O)c2ccc(c(c2)NC(=O)C(CCCNC(=N)N)N)N
• Formula: C23 H31 N7 O5
• Name: methyl N-[4-amino-3-(L-arginylamino)benzene-1-carbonyl]-L-tyrosinate
• ChEMBL: CHEMBL3416696
• ZINC: ZINC000299860352
• PDB chain: 5k1v Chain A Residue 1002

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5k1v Crystal Structures of ERAP2 Complexed with Inhibitors Reveal Pharmacophore Requirements for Optimizing Inhibitor Potency.
• Resolution: 2.897 Å
• Binding residue (original residue number in PDB): D198 E200 P333 G334 A335 E337 H370 E371 H374 E393 D451 E452 Y455 Y892
• Binding residue (residue number reindexed from 1): D145 E147 P280 G281 A282 E284 H317 E318 H321 E340 D398 E399 Y402 Y828
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=5.70,IC50=2uM
  BindingDB: IC50=518nM

Enzymatic activity

• Catalytic site (original residue number in PDB): E337 H370 E371 H374 E393 Q447 Y455
• Catalytic site (residue number reindexed from 1): E284 H317 E318 H321 E340 Q394 Y402
• 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:5k1v, PDBe:5k1v, PDBj:5k1v
• PDBsum: 5k1v
• PubMed: 28337326
• UniProt: Q6P179|ERAP2_HUMAN Endoplasmic reticulum aminopeptidase 2 (Gene Name=ERAP2)