Structure of PDB 4ngn Chain A Binding Site BS04

Receptor Information

>4ngn Chain A (length=696) Species: 9606 (Homo sapiens)

KHNMKAFLDELKAENIKKFLYNFTQIPHLAGTEQNFQLAKQIQSQWKEFG
LDSVELAHYDVLLSYPNKTHPNYISIINEDGNEIFNTSLFEPPPPGYENV
SDIVPPFSAFSPQGMPEGDLVYVNYARTEDFFKLERDMKINCSGKIVIAR
YGKVFRGNKVKNAQLAGAKGVILYSDPADYFAPGVKSYPDGWNLPGGGVQ
RGNILNLNGAGDPLTPGYPANEYAYRRGIAEAVGLPSIPVHPIGYYDAQK
LLEKMGGSAPPDSSWRGSLKVPYNVGPGFTGNFSTQKVKMHIHSTNEVTR
IYNVIGTLRGAVEPDRYVILGGHRDSWVFGGIDPQSGAAVVHEIVRSFGT
LKKEGWRPRRTILFASWDAEEFGLLGSTEWAEENSRLLQERGVAYINADS
SIEGNYTLRVDCTPLMYSLVHNLTKELKSPDEGFEGKSLYESWTKKSPSP
EFSGMPRISKLGSGNDFEVFFQRLGIASGRARYTKNWETNKFSGYPLYHS
VYETYELVEKFYDPMFKYHLTVAQVRGGMVFELANSIVLPFDCRDYAVVL
RKYADKIYSISMKHPQEMKTYSVSFDSLFSAVKNFTEIASKFSERLQDFD
KSNPIVLRMMNDQLMFLERAFIDPLGLPDRPFYRHVIYAPSSHNKYAGES
FPGIYDALFDIESKVDPSKAWGEVKRQIYVAAFTVQAAAETLSEVA

Ligand information

• Ligand ID: J96
• InChI: InChI=1S/C59H99N7O24S/c67-51(11-4-3-10-50-55-48(44-91-50)65-59(77)66-55)61-16-19-79-22-24-81-26-28-83-30-32-85-34-36-87-38-40-89-42-41-88-39-37-86-35-33-84-31-29-82-27-25-80-23-21-78-18-14-52(68)62-17-20-90-49-9-2-1-7-45(49)43-53(69)60-15-6-5-8-46(56(72)73)63-58(76)64-47(57(74)75)12-13-54(70)71/h1-2,7,9,46-48,50,55H,3-6,8,10-44H2,(H,60,69)(H,61,67)(H,62,68)(H,70,71)(H,72,73)(H,74,75)(H2,63,64,76)(H2,65,66,77)/t46-,47-,48-,50-,55-/m0/s1
• InChIKey: GKXYXVKHEPOANF-KCKUEOPDSA-N
• SMILES:
  OpenEye OEToolkits 1.7.6: c1ccc(c(c1)CC(=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
  OpenEye OEToolkits 1.7.6: c1ccc(c(c1)CC(=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)Cc1ccccc1OCCNC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCCC[C@@H]2SC[C@@H]3NC(=O)N[C@H]23)C(O)=O)C(O)=O
  ACDLabs 12.01: O=C(O)C(NC(=O)NC(C(=O)O)CCCCNC(=O)Cc3ccccc3OCCNC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCCCC1SCC2NC(=O)NC12)CCC(=O)O
  CACTVS 3.385: OC(=O)CC[CH](NC(=O)N[CH](CCCCNC(=O)Cc1ccccc1OCCNC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCCC[CH]2SC[CH]3NC(=O)N[CH]23)C(O)=O)C(O)=O
• Formula: C59 H99 N7 O24 S
• PDB chain: 4ngn Chain A Residue 819

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4ngn Rational design of urea-based glutamate carboxypeptidase II (GCPII) inhibitors as versatile tools for specific drug targeting and delivery.
• Resolution: 1.64 Å
• Binding residue (original residue number in PDB): R210 N257 E424 L428 G518 N519 R534 R536 Y552 H553 K699 Y700
• Binding residue (residue number reindexed from 1): R156 N203 E370 L374 G464 N465 R480 R482 Y498 H499 K645 Y646
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=7.55,Ki=28.1nM

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