3bi1: Difference between revisions
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'''X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a transition state analog of methotrexate-Glu''' | {{Structure | ||
|PDB= 3bi1 |SIZE=350|CAPTION= <scene name='initialview01'>3bi1</scene>, resolution 1.50Å | |||
|SITE= <scene name='pdbsite=AC1:Nag+Binding+Site+For+Residue+A+1755'>AC1</scene>, <scene name='pdbsite=AC2:Nag+Binding+Site+For+Residue+A+1756'>AC2</scene>, <scene name='pdbsite=AC3:Nag+Binding+Site+For+Residue+A+1757'>AC3</scene>, <scene name='pdbsite=AC4:Nag+Binding+Site+For+Residue+A+1758'>AC4</scene>, <scene name='pdbsite=AC5:Nag+Binding+Site+For+Residue+A+1759'>AC5</scene>, <scene name='pdbsite=AC6:Nag+Binding+Site+For+Residue+A+1760'>AC6</scene>, <scene name='pdbsite=AC7:Nag+Binding+Site+For+Residue+A+1761'>AC7</scene>, <scene name='pdbsite=AC8:Nag+Binding+Site+For+Residue+A+1762'>AC8</scene>, <scene name='pdbsite=AC9:Nag+Binding+Site+For+Residue+A+1763'>AC9</scene>, <scene name='pdbsite=BC1:Nag+Binding+Site+For+Residue+A+1764'>BC1</scene>, <scene name='pdbsite=BC2:Bma+Binding+Site+For+Residue+A+1765'>BC2</scene>, <scene name='pdbsite=BC3:Man+Binding+Site+For+Residue+A+1766'>BC3</scene>, <scene name='pdbsite=BC4:Zn+Binding+Site+For+Residue+A+1751'>BC4</scene>, <scene name='pdbsite=BC5:Zn+Binding+Site+For+Residue+A+1752'>BC5</scene>, <scene name='pdbsite=BC6:Ca+Binding+Site+For+Residue+A+1753'>BC6</scene>, <scene name='pdbsite=BC7:Cl+Binding+Site+For+Residue+A+1754'>BC7</scene> and <scene name='pdbsite=BC8:3bi+Binding+Site+For+Residue+A+1'>BC8</scene> | |||
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> and <scene name='pdbligand=3BI:'>3BI</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Glutamate_carboxypeptidase_II Glutamate carboxypeptidase II], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.21 3.4.17.21] | |||
|GENE= FOLH1, FOLH, NAALAD1, PSM, PSMA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a transition state analog of methotrexate-Glu''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
3BI1 is a [ | 3BI1 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BI1 OCA]. | ||
==Reference== | ==Reference== | ||
Structural basis of interactions between human glutamate carboxypeptidase II and its substrate analogs., Barinka C, Hlouchova K, Rovenska M, Majer P, Dauter M, Hin N, Ko YS, Tsukamoto T, Slusher BS, Konvalinka J, Lubkowski J, J Mol Biol. 2008 Mar 7;376(5):1438-50. Epub 2008 Jan 5. PMID:[http:// | Structural basis of interactions between human glutamate carboxypeptidase II and its substrate analogs., Barinka C, Hlouchova K, Rovenska M, Majer P, Dauter M, Hin N, Ko YS, Tsukamoto T, Slusher BS, Konvalinka J, Lubkowski J, J Mol Biol. 2008 Mar 7;376(5):1438-50. Epub 2008 Jan 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18234225 18234225] | ||
[[Category: Glutamate carboxypeptidase II]] | [[Category: Glutamate carboxypeptidase II]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:59:03 2008'' | ||
Revision as of 19:59, 20 March 2008
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| , resolution 1.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , , , , , , , , , , , , , , and | ||||||
| Ligands: | , , , and | ||||||
| Gene: | FOLH1, FOLH, NAALAD1, PSM, PSMA (Homo sapiens) | ||||||
| Activity: | Glutamate carboxypeptidase II, with EC number 3.4.17.21 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a transition state analog of methotrexate-Glu
OverviewOverview
Human glutamate carboxypeptidase II (GCPII) is involved in neuronal signal transduction and intestinal folate absorption by means of the hydrolysis of its two natural substrates, N-acetyl-aspartyl-glutamate and folyl-poly-gamma-glutamates, respectively. During the past years, tremendous efforts have been made toward the structural analysis of GCPII. Crystal structures of GCPII in complex with various ligands have provided insight into the binding of these ligands, particularly to the S1' site of the enzyme. In this article, we have extended structural characterization of GCPII to its S1 site by using dipeptide-based inhibitors that interact with both S1 and S1' sites of the enzyme. To this end, we have determined crystal structures of human GCPII in complex with phosphapeptide analogs of folyl-gamma-glutamate, aspartyl-glutamate, and gamma-glutamyl-glutamate, refined at 1.50, 1.60, and 1.67 A resolution, respectively. The S1 pocket of GCPII could be accurately defined and analyzed for the first time, and the data indicate the importance of Asn519, Arg463, Arg534, and Arg536 for recognition of the penultimate (i.e., P1) substrate residues. Direct interactions between the positively charged guanidinium groups of Arg534 and Arg536 and a P1 moiety of a substrate/inhibitor provide mechanistic explanation of GCPII preference for acidic dipeptides. Additionally, observed conformational flexibility of the Arg463 and Arg536 side chains likely regulates GCPII affinity toward different inhibitors and modulates GCPII substrate specificity. The biochemical experiments assessing the hydrolysis of several GCPII substrate derivatives modified at the P1 position, also included in this report, further complement and extend conclusions derived from the structural analysis. The data described here form an a solid foundation for the structurally aided design of novel low-molecular-weight GCPII inhibitors and imaging agents.
About this StructureAbout this Structure
3BI1 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis of interactions between human glutamate carboxypeptidase II and its substrate analogs., Barinka C, Hlouchova K, Rovenska M, Majer P, Dauter M, Hin N, Ko YS, Tsukamoto T, Slusher BS, Konvalinka J, Lubkowski J, J Mol Biol. 2008 Mar 7;376(5):1438-50. Epub 2008 Jan 5. PMID:18234225
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Glutamate carboxypeptidase II
- Homo sapiens
- Single protein
- Barinka, C.
- Lubkowski, J.
- 3BI
- CA
- CL
- NAG
- ZN
- Alternative splicing
- Cytoplasm
- Dipeptidase
- Folate hydrolase
- Glutamate carboxypeptidase ii
- Glycoprotein
- Metal-binding
- Metallopeptidase
- Metalloprotease
- Multifunctional enzyme
- Naaladase
- Polymorphism
- Prostate specific membrane antigen
- Protease
- Signal-anchor
- Transmembrane
- Zinc