Structure of PDB 4mcr Chain A Binding Site BS04

Receptor Information

>4mcr Chain A (length=693) Species: 9606 (Homo sapiens)

HNMKAFLDELKAENIKKFLYNFTQIPHLAGTEQNFQLAKQIQSQWKEFGL
DSVELAHYDVLLSYPNKTHPNYISIINEDGNEIFNTSLFEPPPPGYENVS
DIVPPFSAFSPQGMPEGDLVYVNYARTEDFFKLERDMKINCSGKIVIARY
GKVFRGNKVKNAQLAGAKGVILYSDPADYFAPGVKSYPDGWNLPGGGVQR
GNILNLNGAGDPLTPGYPANEYAYRRGIAEAVGLPSIPVHPIGYYDAQKL
LEKMGGSAPPDSSWRGSLKVPYNVGPGFTGNFSTQKVKMHIHSTNEVTRI
YNVIGTLRGAVEPDRYVILGGHRDSWVFGGIDPQSGAAVVHEIVRSFGTL
KKEGWRPRRTILFASWDAAEFGLLGSTEWAEENSRLLQERGVAYINADSS
IEGNYTLRVDCTPLMYSLVHNLTKELKSPDEGFEGKSLYESWTKKSPSPE
FSGMPRISKLGSGNDFEVFFQRLGIASGRARYTKNWETNKFSGYPLYHSV
YETYELVEKFYDPMFKYHLTVAQVRGGMVFELANSIVLPFDCRDYAVVLR
KYADKIYSISMKHPQEMKTYSVSFDSLFSAVKNFTEIASKFSERLQDFSN
PIVLRMMNDQLMFLERAFIDPLGLPDRPFYRHVIYAPSSHNKYAGESFPG
IYDALFDIESKVDPSKAWGEVKRQIYVAAFTVQAAAETLSEVA

Ligand information

• Ligand ID: 29D
• InChI: InChI=1S/C34H40N10O15/c35-34-43-27-26(29(51)44-34)38-17(14-37-27)13-36-16-3-1-15(2-4-16)28(50)42-21(33(58)59)7-11-24(47)40-19(31(54)55)5-9-22(45)39-18(30(52)53)6-10-23(46)41-20(32(56)57)8-12-25(48)49/h1-4,14,18-21,36H,5-13H2,(H,39,45)(H,40,47)(H,41,46)(H,42,50)(H,48,49)(H,52,53)(H,54,55)(H,56,57)(H,58,59)(H3,35,37,43,44,51)/t18-,19-,20-,21-/m0/s1
• InChIKey: YMUKRFYNHZWDBN-TUFLPTIASA-N
• SMILES:
  ACDLabs 12.01: O=C(O)C(NC(=O)CCC(C(=O)O)NC(=O)CCC(C(=O)O)NC(=O)CCC(C(=O)O)NC(=O)c1ccc(cc1)NCc3nc2c(N=C(N)NC2=O)nc3)CCC(=O)O
  CACTVS 3.385: NC1=Nc2ncc(CNc3ccc(cc3)C(=O)N[CH](CCC(=O)N[CH](CCC(=O)N[CH](CCC(=O)N[CH](CCC(O)=O)C(O)=O)C(O)=O)C(O)=O)C(O)=O)nc2C(=O)N1
  CACTVS 3.385: NC1=Nc2ncc(CNc3ccc(cc3)C(=O)N[C@@H](CCC(=O)N[C@@H](CCC(=O)N[C@@H](CCC(=O)N[C@@H](CCC(O)=O)C(O)=O)C(O)=O)C(O)=O)C(O)=O)nc2C(=O)N1
  OpenEye OEToolkits 1.7.6: c1cc(ccc1C(=O)NC(CCC(=O)NC(CCC(=O)NC(CCC(=O)NC(CCC(=O)O)C(=O)O)C(=O)O)C(=O)O)C(=O)O)NCc2cnc3c(n2)C(=O)NC(=N3)N
  OpenEye OEToolkits 1.7.6: c1cc(ccc1C(=O)N[C@@H](CCC(=O)N[C@@H](CCC(=O)N[C@@H](CCC(=O)N[C@@H](CCC(=O)O)C(=O)O)C(=O)O)C(=O)O)C(=O)O)NCc2cnc3c(n2)C(=O)NC(=N3)N
• Formula: C34 H40 N10 O15
• Name: N-(4-{[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino}benzoyl)-L-gamma-glutamyl-L-gamma-glutamyl-L-gamma-glutamyl-L-glutamic acid
• ZINC: ZINC000085573795
• PDB chain: 4mcr Chain A Residue 818

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4mcr Structural and biochemical characterization of the folyl-poly-gamma-l-glutamate hydrolyzing activity of human glutamate carboxypeptidase II.
• Resolution: 1.65 Å
• Binding residue (original residue number in PDB): R210 E425 R511 S513 G518 N519 R534 W541 E542 Y552 H553 K699 Y700 A701
• Binding residue (residue number reindexed from 1): R155 E370 R456 S458 G463 N464 R479 W486 E487 Y497 H498 K642 Y643 A644
• Annotation score: 1

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:4mcr, PDBe:4mcr, PDBj:4mcr
• PDBsum: 4mcr
• PubMed: 24863754
• UniProt: Q04609|FOLH1_HUMAN Glutamate carboxypeptidase 2 (Gene Name=FOLH1)