Structure of PDB 3mdj Chain B Binding Site BS02

Receptor Information

>3mdj Chain B (length=821) Species: 9606 (Homo sapiens)

PFPWNKIRLPEYVIPVHYDLLIHANLTTLTFWGTTKVEITASQPTSTIIL
HSHHLQISRATLRKGAGERLSEEPLQVLEHPRQEQIALLAPEPLLVGLPY
TVVIHYAGNLSETFHGFYKSTYRTKEGELRILASTQFEPTAARMAFPCFD
EPAFKASFSIKIRREPRHLAISNMPLVKSVTVAEGLIEDHFDVTVKMSTY
LVAFIISDFESVSKITKSGVKVSVYAVPDKINQADYALDAAVTLLEFYED
YFSIPYPLPKQDLAAIPDFQSGAMENWGLTTYRESALLFDAEKSSASSKL
DITMTVAHELAHQWFGNLVTMEWWNDLWLNEGFAKFMEFVSVSVTHPELK
VGDYFFGKCFDAMEVDALNSSDDVSYDKGACILNMLREYLSADAFKSGIV
QYLQKHSYKNTKNEDLWDSMASIVDVKTMMNTWTLQRGFPLITITVRGRN
VHMKQEHYMKAPDTGYLWHVPLTFITSKSDMVHRFLLKTKTDVLILPEEV
EWIKFNVGMNGYYIVHYEDDGWDSLTGLLKGTHTAVSSNDRASLINNAFQ
LVSIGKLSIEKALDLSLYLKHETEIMPVFQGLNELIPMYKLMEKRDMNEV
ETQFKAFLIRLLRDLIDKQTWTDEGSVSERMLRSELLLLACVHNYQPCVQ
RAEGYFRKWKESNGNLSLPVDVTLAVFAVGAQSTEGWDFLYSKYQFSLSS
TEKSQIEFALCRTQNKEKLQWLLDESFKGDKIKTQEFPQILTLIGRNPVG
YPLAWQFLRKNWNKLVQKSSSIAHMVMGTTNQFSTRTRLEEVKCVQQTIE
TIEENIGWMDKNFDKIRVWLQ

Ligand information

• Ligand ID: BES
• InChI: InChI=1S/C16H24N2O4/c1-10(2)8-13(16(21)22)18-15(20)14(19)12(17)9-11-6-4-3-5-7-11/h3-7,10,12-14,19H,8-9,17H2,1-2H3,(H,18,20)(H,21,22)/t12-,13+,14+/m1/s1
• InChIKey: VGGGPCQERPFHOB-RDBSUJKOSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: CC(C)C[C@@H](C(=O)O)NC(=O)[C@H]([C@@H](Cc1ccccc1)N)O
  CACTVS 3.341: CC(C)C[C@H](NC(=O)[C@@H](O)[C@H](N)Cc1ccccc1)C(O)=O
  ACDLabs 10.04: O=C(O)C(NC(=O)C(O)C(N)Cc1ccccc1)CC(C)C
  OpenEye OEToolkits 1.5.0: CC(C)CC(C(=O)O)NC(=O)C(C(Cc1ccccc1)N)O
  CACTVS 3.341: CC(C)C[CH](NC(=O)[CH](O)[CH](N)Cc1ccccc1)C(O)=O
• Formula: C16 H24 N2 O4
• Name: 2-(3-AMINO-2-HYDROXY-4-PHENYL-BUTYRYLAMINO)-4-METHYL-PENTANOIC ACID;
  BESTATIN
• ChEMBL: CHEMBL29292
• DrugBank: DB03424
• ZINC: ZINC000001542895
• PDB chain: 3mdj Chain B Residue 1001

Receptor-Ligand Complex Structure

Structure summary

• PDB: 3mdj Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1.
• Resolution: 2.95 Å
• Binding residue (original residue number in PDB): Q181 E183 S316 A318 M319 E320 H353 E354 E376 K380
• Binding residue (residue number reindexed from 1): Q136 E138 S271 A273 M274 E275 H308 E309 E331 K335
• Annotation score: 3
• Binding affinity: BindingDB: IC50=50000nM

Enzymatic activity

• Catalytic site (original residue number in PDB): E320 H353 E354 H357 E376 Y438
• Catalytic site (residue number reindexed from 1): E275 H308 E309 H312 E331 Y376
• 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:3mdj, PDBe:3mdj, PDBj:3mdj
• PDBsum: 3mdj
• PubMed: 21478864
• UniProt: Q9NZ08|ERAP1_HUMAN Endoplasmic reticulum aminopeptidase 1 (Gene Name=ERAP1)