PDBsum entry 4x3r

Hydrolase

PDB id: 4x3r

Contents

Protein chain

690 a.a.

Ligands

NAG-NAG ×3

NAG-NAG-BMA

NAG-NAG-BMA-MAN

NAG ×2

686

Metals

_ZN ×2

_CL

_CA

Waters ×634

PDB id:

4x3r

Name:

Hydrolase

Title:

Avi-gcpii structure in complex with fitc-conjugated gcpii-specific inhibitor

Structure:

Glutamate carboxypeptidase 2. Chain: a. Fragment: avi-tagged extracellular portion, unp residues 44-750. Synonym: cell growth-inhibiting gene 27 protein,folate hydrolase 1, folylpoly-gamma-glutamate carboxypeptidase,fgcp,glutamate carboxypeptidase ii,gcpii,membrane glutamate carboxypeptidase,mgcp,n- acetylated-alpha-linked acidic dipeptidase i,naaladase i,prostate- specific membrane antigen,psma,pteroylpoly-gamma-glutamate carboxypeptidase.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: folh1, folh, naalad1, psm, psma, gig27. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Expression_system_cell_line: schneider s2 cells

Resolution:

1.86Å R-factor: 0.149 R-free: 0.180

Authors:

J.Tykvart,J.Konvalinka

Key ref:

J.Tykvart et al. (2015). Design of highly potent urea-based, exosite-binding inhibitors selective for glutamate carboxypeptidase II. J Med Chem, 58, 4357-4363. PubMed id: 25923815 DOI: 10.1021/acs.jmedchem.5b00278

Date:

01-Dec-14 Release date: 14-Oct-15

Protein chain

Q04609  (FOLH1_HUMAN) -  Glutamate carboxypeptidase 2 from Homo sapiens

Seq: 750 a.a.

Struc: 690 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.17.21 - glutamate carboxypeptidase Ii.
• Reaction: Release of an unsubstituted, C-terminal glutamyl residue, typically from Ac-Asp-Glu or folylpoly-gamma-glutamates.
• Cofactor: Zn(2+)

DOI no: 10.1021/acs.jmedchem.5b00278

J Med Chem 58:4357-4363 (2015)

PubMed id: 25923815

Design of highly potent urea-based, exosite-binding inhibitors selective for glutamate carboxypeptidase II.

J.Tykvart, J.Schimer, A.Jančařík, J.Bařinková, V.Navrátil, J.Starková, K.Šrámková, J.Konvalinka, P.Majer, P.Šácha.

ABSTRACT

We present here a structure-aided design of inhibitors targeting the active site as well as exosites of glutamate carboxypeptidase II (GCPII), a prostate cancer marker, preparing potent and selective inhibitors that are more than 1000-fold more active toward GCPII than its closest human homologue, glutamate carboxypeptidase III (GCPIII). Additionally, we demonstrate that the prepared inhibitor conjugate can be used for sensitive and selective imaging of GCPII in mammalian cells.