Structure of PDB 4ngp Chain A Binding Site BS01

Receptor Information

>4ngp Chain A (length=695) Species: 9606 (Homo sapiens)

KHNMKAFLDELKAENIKKFLYNFTQIPHLAGTEQNFQLAKQIQSQWKEFG
LDSVELAHYDVLLSYPNKTHPNYISIINEDGNEIFNTSLFEPPPPGYENV
SDIVPPFSAFSPQGMPEGDLVYVNYARTEDFFKLERDMKINCSGKIVIAR
YGKVFRGNKVKNAQLAGAKGVILYSDPADYFAPGVKSYPDGWNLPGGGVQ
RGNILNLNGAGDPLTPGYPANEYAYRRGIAEAVGLPSIPVHPIGYYDAQK
LLEKMGGSAPPDSSWRGSLKVPYNVGPGFTGNFSTQKVKMHIHSTNEVTR
IYNVIGTLRGAVEPDRYVILGGHRDSWVFGGIDPQSGAAVVHEIVRSFGT
LKKEGWRPRRTILFASWDAEEFGLLGSTEWAEENSRLLQERGVAYINADS
SIEGNYTLRVDCTPLMYSLVHNLTKELKSPDEGFEGKSLYESWTKKSPSP
EFSGMPRISKLGSGNDFEVFFQRLGIASGRARYTKNWETNKFSGYPLYHS
VYETYELVEKFYDPMFKYHLTVAQVRGGMVFELANSIVLPFDCRDYAVVL
RKYADKIYSISMKHPQEMKTYSVSFDSLFSAVKNFTEIASKFSERLQDFD
KNPIVLRMMNDQLMFLERAFIDPLGLPDRPFYRHVIYAPSSHNKYAGESF
PGIYDALFDIESKVDPSKAWGEVKRQIYVAAFTVQAAAETLSEVA

Ligand information

• Ligand ID: J31
• InChI: InChI=1S/C58H97N7O24S/c66-50(11-4-3-10-49-53-47(43-90-49)64-58(76)65-53)59-16-19-78-22-24-80-26-28-82-30-32-84-34-36-86-38-40-88-42-41-87-39-37-85-35-33-83-31-29-81-27-25-79-23-21-77-18-14-51(67)60-17-20-89-48-9-2-1-7-44(48)54(70)61-15-6-5-8-45(55(71)72)62-57(75)63-46(56(73)74)12-13-52(68)69/h1-2,7,9,45-47,49,53H,3-6,8,10-43H2,(H,59,66)(H,60,67)(H,61,70)(H,68,69)(H,71,72)(H,73,74)(H2,62,63,75)(H2,64,65,76)/t45-,46-,47-,49-,53-/m0/s1
• InChIKey: ULKCTSJOJRHWDD-HJXABITDSA-N
• SMILES:
  OpenEye OEToolkits 1.7.6: c1ccc(c(c1)C(=O)NCCCCC(C(=O)O)NC(=O)NC(CCC(=O)O)C(=O)O)OCCNC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCCCC2C3C(CS2)NC(=O)N3
  CACTVS 3.385: OC(=O)CC[C@H](NC(=O)N[C@@H](CCCCNC(=O)c1ccccc1OCCNC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCCC[C@@H]2SC[C@@H]3NC(=O)N[C@H]23)C(O)=O)C(O)=O
  OpenEye OEToolkits 1.7.6: c1ccc(c(c1)C(=O)NCCCC[C@@H](C(=O)O)NC(=O)N[C@@H](CCC(=O)O)C(=O)O)OCCNC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCCC[C@H]2[C@@H]3[C@H](CS2)NC(=O)N3
  CACTVS 3.385: OC(=O)CC[CH](NC(=O)N[CH](CCCCNC(=O)c1ccccc1OCCNC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCCC[CH]2SC[CH]3NC(=O)N[CH]23)C(O)=O)C(O)=O
  ACDLabs 12.01: O=C(O)C(NC(=O)NC(C(=O)O)CCCCNC(=O)c3ccccc3OCCNC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCCCC1SCC2NC(=O)NC12)CCC(=O)O
• Formula: C58 H97 N7 O24 S
• ChEMBL: CHEMBL3309673
• PDB chain: 4ngp Chain A Residue 817

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4ngp Rational design of urea-based glutamate carboxypeptidase II (GCPII) inhibitors as versatile tools for specific drug targeting and delivery.
• Resolution: 1.63 Å
• Binding residue (original residue number in PDB): R210 E424 L428 E457 R463 G518 N519 R536 W541 N544 F546 Y552 H553 K699 Y700 A701
• Binding residue (residue number reindexed from 1): R156 E370 L374 E403 R409 G464 N465 R482 W487 N490 F492 Y498 H499 K644 Y645 A646
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=7.96,Ki=10.97nM
  BindingDB: Ki=11nM

Enzymatic activity

• Enzyme Commision number: 3.4.17.21: glutamate carboxypeptidase II.

Gene Ontology

Molecular Function

• GO:0004180 carboxypeptidase activity
• GO:0004181 metallocarboxypeptidase activity
• GO:0008233 peptidase activity
• GO:0008237 metallopeptidase activity
• GO:0016805 dipeptidase activity
• GO:0046872 metal ion binding
• GO:1904492 Ac-Asp-Glu binding
• GO:1904493 tetrahydrofolyl-poly(glutamate) polymer binding

Biological Process

• GO:0006508 proteolysis
• GO:0006760 folic acid-containing compound metabolic process
• GO:0035609 C-terminal protein deglutamylation

Cellular Component

• GO:0005737 cytoplasm
• GO:0005886 plasma membrane
• GO:0009986 cell surface
• GO:0016020 membrane
• GO:0070062 extracellular exosome

External links

• PDB: RCSB:4ngp, PDBe:4ngp, PDBj:4ngp
• PDBsum: 4ngp
• PubMed: 24954515
• UniProt: Q04609|FOLH1_HUMAN Glutamate carboxypeptidase 2 (Gene Name=FOLH1)