Structure of PDB 7z28 Chain A Binding Site BS02

Receptor Information

>7z28 Chain A (length=859) Species: 9606 (Homo sapiens)

TPFPWNKIRLPEYVIPVHYDLLIHANLTTLTFWGTTKVEITASQPTSTII
LHSHHLQISRATLRKGAGERLSEEPLQVLEHPRQEQIALLAPEPLLVGLP
YTVVIHYAGNLSETFHGFYKSTYRTKEGELRILASTQFEPTAARMAFPCF
DEPAFKASFSIKIRREPRHLAISNMPLVKSVTVAEGLIEDHFDVTVKMST
YLVAFIISDFESVSKITKSGVKVSVYAVPDKINQADYALDAAVTLLEFYE
DYFSIPYPLPKQDLAAIPDFQSGAMENWGLTTYRESALLFDAEKSSASSK
LGITMTVAHELAHQWFGNLVTMEWWNDLWLNEGFAKFMEFVSVSVTHPEL
KVGDYFFGKCFDAMEVDALNSSHPVSTPVENPAQIREMFDDVSYDKGACI
LNMLREYLSADAFKSGIVQYLQKHSYKNTKNEDLWDSMASISGDVKTMMN
TWTLQKGFPLITITVRGRNVHMKQEHYMKGDTGYLWHVPLTFITSKSDMV
HRFLLKTKTDVLILPEEVEWIKFNVGMNGYYIVHYEDDGWDSLTGLLKGT
HTAVSSNDRASLINNAFQLVSIGKLSIEKALDLSLYLKHETEIMPVFQGL
NELIPMYKLMEKRDMNEVETQFKAFLIRLLRDLIDKQTWTDEGSVSERML
RSQLLLLACVHNYQPCVQRAEGYFRKWKESNGNLSLPVDVTLAVFAVGAQ
STEGWDFLYSKYQFSLSSTEKSQIEFALCRTQNKEKLQWLLDESFKGDKI
KTQEFPQILTLIGRNPVGYPLAWQFLRKNWNKLVQKFELGSSSIAHMVMG
TTNQFSTRTRLEEVKGFFSSLKENGSQLRCVQQTIETIEENIGWMDKNFD
KIRVWLQSE

Ligand information

• Ligand ID: I88
• InChI: InChI=1S/C23H37N3O7/c1-14(2)12-18(25-22(31)20(29)17(24)6-4-5-11-27)21(30)26-19(23(32)33-3)13-15-7-9-16(28)10-8-15/h7-10,14,17-20,27-29H,4-6,11-13,24H2,1-3H3,(H,25,31)(H,26,30)/t17-,18+,19+,20+/m1/s1
• InChIKey: LCFWQIPNOMDXPJ-FYQPLNBISA-N
• SMILES:
  CACTVS 3.385: COC(=O)[CH](Cc1ccc(O)cc1)NC(=O)[CH](CC(C)C)NC(=O)[CH](O)[CH](N)CCCCO
  CACTVS 3.385: COC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](O)[C@H](N)CCCCO
  OpenEye OEToolkits 2.0.7: CC(C)C[C@@H](C(=O)N[C@@H](Cc1ccc(cc1)O)C(=O)OC)NC(=O)[C@H]([C@@H](CCCCO)N)O
  OpenEye OEToolkits 2.0.7: CC(C)CC(C(=O)NC(Cc1ccc(cc1)O)C(=O)OC)NC(=O)C(C(CCCCO)N)O
• Formula: C23 H37 N3 O7
• Name: methyl (2~{S})-2-[[(2~{S})-2-[[(2~{S},3~{R})-3-azanyl-2,7-bis(oxidanyl)heptanoyl]amino]-4-methyl-pentanoyl]amino]-3-(4-hydroxyphenyl)propanoate
• ChEMBL: CHEMBL5194823
• PDB chain: 7z28 Chain A Residue 1003

Receptor-Ligand Complex Structure

Structure summary

• PDB: 7z28 Discovery of Selective Nanomolar Inhibitors for Insulin-Regulated Aminopeptidase Based on alpha-Hydroxy-beta-amino Acid Derivatives of Bestatin.
• Resolution: 1.55 Å
• Binding residue (original residue number in PDB): E183 S316 G317 A318 M319 E320 T350 H353 E354 H357 E376 F433 Y438 S869 S870 H873
• Binding residue (residue number reindexed from 1): E139 S272 G273 A274 M275 E276 T306 H309 E310 H313 E332 F389 Y394 S792 S793 H796
• Annotation score: 1

Enzymatic activity

• Enzyme Commision number: 3.4.11.-

Gene Ontology

Molecular Function

• GO:0004175 endopeptidase activity
• GO:0004177 aminopeptidase activity
• GO:0005138 interleukin-6 receptor binding
• GO:0005151 interleukin-1, type II receptor binding
• GO:0005515 protein binding
• GO:0008233 peptidase activity
• GO:0008235 metalloexopeptidase activity
• 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:0001525 angiogenesis
• GO:0002250 adaptive immune response
• GO:0002474 antigen processing and presentation of peptide antigen via MHC class I
• GO:0006508 proteolysis
• GO:0006509 membrane protein ectodomain proteolysis
• GO:0008217 regulation of blood pressure
• GO:0009617 response to bacterium
• GO:0019885 antigen processing and presentation of endogenous peptide antigen via MHC class I
• GO:0043171 peptide catabolic process
• GO:0045088 regulation of innate immune response
• GO:0045444 fat cell differentiation
• GO:0045766 positive regulation of angiogenesis

Cellular Component

• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:0005737 cytoplasm
• GO:0005783 endoplasmic reticulum
• GO:0005788 endoplasmic reticulum lumen
• GO:0005789 endoplasmic reticulum membrane
• GO:0005829 cytosol
• GO:0016020 membrane
• GO:0070062 extracellular exosome

External links

• PDB: RCSB:7z28, PDBe:7z28, PDBj:7z28
• PDBsum: 7z28
• PubMed: 35833347
• UniProt: Q9NZ08|ERAP1_HUMAN Endoplasmic reticulum aminopeptidase 1 (Gene Name=ERAP1)