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PDBsum entry 2jbk
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Contents |
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Membrane-bound glutamate carboxypeptidase ii (gcpii) in complex with quisqualic acid (quisqualate, alpha-amino-3,5-dioxo-1,2,4- oxadiazolidine-2-propanoic acid)
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Structure:
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Glutamate carboxypeptidase 2. Chain: a. Fragment: extracellular part, residues 44-750. Synonym: membrane glutamate carboxypeptidase, mgcp, n-acetylated- alpha-linked acidic dipeptidase i, naaladase i, pteroylpoly-gamma- glutamate carboxypeptidase, folylpoly-gamma-glutamate carboxypeptidase, fgcp, folate hydrolase 1, psm, prostate- specific membrane antigen, psma, glutamate carboxypeptidase ii. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Organ: brain. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Expression_system_cell_line: schneider's cells
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Resolution:
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Authors:
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J.R.Mesters,K.Henning,R.Hilgenfeld
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Key ref:
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J.R.Mesters
et al.
(2007).
Human glutamate carboxypeptidase II inhibition: structures of GCPII in complex with two potent inhibitors, quisqualate and 2-PMPA.
Acta Crystallogr D Biol Crystallogr,
63,
508-513.
PubMed id:
DOI:
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Date:
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07-Dec-06
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Release date:
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18-Dec-06
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PROCHECK
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Headers
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References
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Q04609
(FOLH1_HUMAN) -
Glutamate carboxypeptidase 2 from Homo sapiens
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Seq:
Struc:
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750 a.a.
687 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.3.4.17.21
- glutamate carboxypeptidase Ii.
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Reaction:
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Release of an unsubstituted, C-terminal glutamyl residue, typically from Ac-Asp-Glu or folylpoly-gamma-glutamates.
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Cofactor:
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Zn(2+)
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DOI no:
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Acta Crystallogr D Biol Crystallogr
63:508-513
(2007)
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PubMed id:
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Human glutamate carboxypeptidase II inhibition: structures of GCPII in complex with two potent inhibitors, quisqualate and 2-PMPA.
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J.R.Mesters,
K.Henning,
R.Hilgenfeld.
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ABSTRACT
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Human glutamate carboxypeptidase II (GCPII) occurs in the central nervous system
as well as in human prostate (where it is called prostate-specific membrane
antigen; PSMA). Inhibitors of the enzyme have been shown to provide
neuroprotection, but may also be useful for the detection, imaging and treatment
of prostate cancer. Crystal structures were determined of the extracellular part
of GCPII (amino-acid residues 44-750) in complex with two potent inhibitors,
quisqualate and 2-PMPA (the strongest GCPII inhibitor to date), at resolutions
of 3.0 and 2.2 A, respectively. In addition, models were constructed for binding
of the inhibitors willardiine, homoibotenate, L-2-amino-4-phosphonobutanoic acid
and L-serine-O-sulfate to the S1' site of the enzyme. The common denominator for
high-affinity binding to the S1' site is the formation of two strong salt
bridges.
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Selected figure(s)
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Figure 1.
Figure 1 (a) Binding mode of glutamate to the S1' pocket of
GCPII. (b)-(g) Chemical formulae of 2-PMPA (b), L-AP4 (c), L-SOS
(d), quisqualate (e), HIBO (f) and willardiine (g).
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The above figure is
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2007,
63,
508-513)
copyright 2007.
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Figure was
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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B.R.Blank,
P.Alayoglu,
W.Engen,
J.K.Choi,
C.E.Berkman,
and
M.O.Anderson
(2011).
N-Substituted Glutamyl Sulfonamides as Inhibitors of Glutamate Carboxypeptidase II (GCP2).
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Chem Biol Drug Des,
77,
241-247.
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Y.Chen,
C.A.Foss,
Y.Byun,
S.Nimmagadda,
M.Pullambhatla,
J.J.Fox,
M.Castanares,
S.E.Lupold,
J.W.Babich,
R.C.Mease,
and
M.G.Pomper
(2008).
Radiohalogenated prostate-specific membrane antigen (PSMA)-based ureas as imaging agents for prostate cancer.
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J Med Chem,
51,
7933-7943.
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T.Tsukamoto,
K.M.Wozniak,
and
B.S.Slusher
(2007).
Progress in the discovery and development of glutamate carboxypeptidase II inhibitors.
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Drug Discov Today,
12,
767-776.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
