PDBsum entry: 2oot

Hydrolase

PDB id: 2oot

Contents

Protein chain

686 a.a. *

Ligands

NAG-NAG ×2

NAG ×4

NAG-NAG-BMA-MAN

Metals

_CL

_ZN ×2

_CA

Waters ×561

* Residue conservation analysis

PDB id:

2oot

Name:

Hydrolase

Title:

A high resolution structure of ligand-free human glutamate carboxypeptidase ii

Structure:

Glutamate carboxypeptidase 2. Chain: a. Fragment: residues 44-750. Synonym: glutamate carboxypeptidase ii, membrane glutamate carboxypeptidase, mgcp, n- acetylated-alpha-linked acidic d i, naaladase i, pteroylpoly-gamma-glutamate carboxypeptidas folylpoly-gamma- glutamate carboxypeptidase, fgcp, folate h 1, prostate- specific membrane antigen, psma, psm. Engineered: yes

Source:

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

Resolution:

1.64Å R-factor: 0.207 R-free: 0.228

Authors:

C.Barinka,J.Lubkowski

Key ref:

C.Barinka et al. (2007). A high-resolution structure of ligand-free human glutamate carboxypeptidase II. Acta Crystallograph Sect F Struct Biol Cryst Commun, 63, 150-153. PubMed id: 17329803 Ref: Full text

Date:

26-Jan-07 Release date: 20-Mar-07

Protein chain

Q04609  (FOLH1_HUMAN) -  Glutamate carboxypeptidase 2

Seq: 750 a.a.

Struc: 686 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: Zinc

 Gene Ontology (GO) functional annotation 

• Cellular component: membrane (7 terms)
• Biological process: metabolic process (3 terms)
• Biochemical function: catalytic activity (7 terms)

Full text	Acta Crystallograph Sect F Struct Biol Cryst Commun 63:150-153 (2007)
PubMed id: 17329803

A high-resolution structure of ligand-free human glutamate carboxypeptidase II.

C.Barinka, J.Starkova, J.Konvalinka, J.Lubkowski.

ABSTRACT

Human glutamate carboxypeptidase II (GCPII; EC 3.4.17.21) is an established marker for prostate-cancer diagnosis as well as a candidate therapeutic target for the treatment of diverse pathologies that involve glutamatergic transmission. Structural data on GCPII are thus valuable for the design and optimization of GCPII-specific inhibitors and diagnostic probes. The currently available structure of ligand-free GCPII was refined to a resolution of 3.5 A. This work reports the structure of the protein refined to 1.65 A resolution, with crystallographic values of R = 0.207 and R(free) = 0.228. The new structure extends the resolution appreciably and the new model based on this data shows significant differences when compared with the previously published model.

Selected figure(s)

Figure 1.
Ensemble of conformations of the 'glutarate sensor'. Two residues in this segment, Lys699 and Tyr700, interact directly with the ligands of the S1[prime prime or minute] site. The GCPII structures available from the PDB were superimposed on the structure of rhGCPII[new]. The C^[alpha] traces are shown in ribbon representation, the active-site Zn^+2 ions are shown as blue spheres and the yellow sphere represents the S1-bound Cl^[minus sign] ion. The 'glutarate sensor' is shown in yellow for PDB entry 1z8l, in magenta for 2c6g, in blue for 2c6p and in red and cyan for the two conformations in rhGCPII[new]. The S1 and S1[prime prime or minute] sites are highlighted by gray ellipses. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 March 1; 63(Pt 3): 150–153. Published online 2007 February 13. doi: 10.1107/S174430910700379X. Copyright [copyright] International Union of Crystallography 2007

Figure 2.
Organization of the positively charged arginine stack in the putative S1 pocket. Arg463, Arg534 and Arg536 are located within the antiparallel [beta]-strands ([beta]14, Ser532 --Thr538; [beta]13, Thr461 --Cys466). In the rhGCPII[new] structure, Arg463 and Arg534 are present in single conformations, while Arg536 adopts two alternate conformations. The S1-bound Cl^[minus sign] ion (shown as a yellow sphere) stabilizes the invariant conformation of Arg534 as well as neutralizing the positive charge contributed by the Arg534 and Arg536 guanidinium groups. The side chains of Ser454, Asp465 and Arg536 are shown in two alternate conformations and the active-site Zn^+2 ions are represented as blue spheres. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 March 1; 63(Pt 3): 150–153. Published online 2007 February 13. doi: 10.1107/S174430910700379X. Copyright [copyright] International Union of Crystallography 2007

The above figures are reprinted from an Open Access publication published by the IUCr: Acta Crystallograph Sect F Struct Biol Cryst Commun (2007, 63, 150-153) copyright 2007.