3bi0
From Proteopedia
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|PDB= 3bi0 |SIZE=350|CAPTION= <scene name='initialview01'>3bi0</scene>, resolution 1.67Å | |PDB= 3bi0 |SIZE=350|CAPTION= <scene name='initialview01'>3bi0</scene>, resolution 1.67Å | ||
|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+1767'>AC5</scene>, <scene name='pdbsite=AC6:Nag+Binding+Site+For+Residue+A+1759'>AC6</scene>, <scene name='pdbsite=AC7:Nag+Binding+Site+For+Residue+A+1760'>AC7</scene>, <scene name='pdbsite=AC8:Nag+Binding+Site+For+Residue+A+1761'>AC8</scene>, <scene name='pdbsite=AC9:Nag+Binding+Site+For+Residue+A+1762'>AC9</scene>, <scene name='pdbsite=BC1:Nag+Binding+Site+For+Residue+A+1763'>BC1</scene>, <scene name='pdbsite=BC2:Nag+Binding+Site+For+Residue+A+1764'>BC2</scene>, <scene name='pdbsite=BC3:Bma+Binding+Site+For+Residue+A+1765'>BC3</scene>, <scene name='pdbsite=BC4:Man+Binding+Site+For+Residue+A+1766'>BC4</scene>, <scene name='pdbsite=BC5:Zn+Binding+Site+For+Residue+A+1751'>BC5</scene>, <scene name='pdbsite=BC6:Zn+Binding+Site+For+Residue+A+1752'>BC6</scene>, <scene name='pdbsite=BC7:Ca+Binding+Site+For+Residue+A+1753'>BC7</scene>, <scene name='pdbsite=BC8:Cl+Binding+Site+For+Residue+A+1754'>BC8</scene> and <scene name='pdbsite=BC9:Bix+Binding+Site+For+Residue+A+1'>BC9</scene> | |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+1767'>AC5</scene>, <scene name='pdbsite=AC6:Nag+Binding+Site+For+Residue+A+1759'>AC6</scene>, <scene name='pdbsite=AC7:Nag+Binding+Site+For+Residue+A+1760'>AC7</scene>, <scene name='pdbsite=AC8:Nag+Binding+Site+For+Residue+A+1761'>AC8</scene>, <scene name='pdbsite=AC9:Nag+Binding+Site+For+Residue+A+1762'>AC9</scene>, <scene name='pdbsite=BC1:Nag+Binding+Site+For+Residue+A+1763'>BC1</scene>, <scene name='pdbsite=BC2:Nag+Binding+Site+For+Residue+A+1764'>BC2</scene>, <scene name='pdbsite=BC3:Bma+Binding+Site+For+Residue+A+1765'>BC3</scene>, <scene name='pdbsite=BC4:Man+Binding+Site+For+Residue+A+1766'>BC4</scene>, <scene name='pdbsite=BC5:Zn+Binding+Site+For+Residue+A+1751'>BC5</scene>, <scene name='pdbsite=BC6:Zn+Binding+Site+For+Residue+A+1752'>BC6</scene>, <scene name='pdbsite=BC7:Ca+Binding+Site+For+Residue+A+1753'>BC7</scene>, <scene name='pdbsite=BC8:Cl+Binding+Site+For+Residue+A+1754'>BC8</scene> and <scene name='pdbsite=BC9:Bix+Binding+Site+For+Residue+A+1'>BC9</scene> | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=BIX:(2S)-2-{[(S)-[(3S)-3-AMINO-3-CARBOXYPROPYL](HYDROXY)PHOSPHORYL]METHYL}PENTANEDIOIC+ACID'>BIX</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= FOLH1, FOLH, NAALAD1, PSM, PSMA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= FOLH1, FOLH, NAALAD1, PSM, PSMA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[3bhx|3BHX]], [[3bi1|3BI1]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bi0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bi0 OCA], [http://www.ebi.ac.uk/pdbsum/3bi0 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3bi0 RCSB]</span> | ||
}} | }} | ||
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[[Category: Barinka, C.]] | [[Category: Barinka, C.]] | ||
[[Category: Lubkowski, J.]] | [[Category: Lubkowski, J.]] | ||
| - | [[Category: BIX]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: CL]] | ||
| - | [[Category: NAG]] | ||
| - | [[Category: ZN]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
[[Category: cytoplasm]] | [[Category: cytoplasm]] | ||
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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 Mon Mar 31 05:26:25 2008'' |
Revision as of 02:26, 31 March 2008
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| , resolution 1.67Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , , , , , , , , , , , , , , , and | ||||||
| Ligands: | , , , , , , | ||||||
| Gene: | FOLH1, FOLH, NAALAD1, PSM, PSMA (Homo sapiens) | ||||||
| Activity: | Glutamate carboxypeptidase II, with EC number 3.4.17.21 | ||||||
| Related: | 3BHX, 3BI1
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a transition state analog of Glu-Glu
Overview
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 Structure
3BI0 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
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:18234225
Page seeded by OCA on Mon Mar 31 05:26:25 2008
Categories: Glutamate carboxypeptidase II | Homo sapiens | Single protein | Barinka, C. | Lubkowski, J. | 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
