4mcp

From Proteopedia

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Revision as of 11:58, 5 August 2016

A high resolution structure of human glutamate carboxypeptidase II (GCPII) in complex with folyl-gamma-L-glutamic acid (pteroyldi-gamma-L-glutamic acid)

Structural highlights

4mcp is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , ,
Related:	4mcq, 4mcr, 4mcs
Activity:	Glutamate carboxypeptidase II, with EC number 3.4.17.21
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[FOLH1_HUMAN] Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate. In the brain, modulates excitatory neurotransmission through the hydrolysis of the neuropeptide, N-aceylaspartylglutamate (NAAG), thereby releasing glutamate. Isoform PSM-4 and isoform PSM-5 would appear to be physiologically irrelevant. Involved in prostate tumor progression. Also exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC.

Publication Abstract from PubMed

In addition to its well-characterized role in the central nervous system, human glutamate carboxypeptidase II (GCPII; Uniprot ID Q04609) acts as a folate hydrolase in the small intestine, participating in the absorption of dietary polyglutamylated folates (folyl-n-gamma-l-glutamic acid), which are the provitamin form of folic acid (also known as vitamin B9 ). Despite the role of GCPII as a folate hydrolase, nothing is known about the processing of polyglutamylated folates by GCPII at the structural or enzymological level. Moreover, many epidemiologic studies on the relationship of the naturally occurring His475Tyr polymorphism to folic acid status suggest that this polymorphism may be associated with several pathologies linked to impaired folate metabolism. In the present study, we report: (a) a series X-ray structures of complexes between a catalytically inactive GCPII mutant (Glu424Ala) and a panel of naturally occurring polyglutamylated folates; (b) the X-ray structure of the His475Tyr variant at a resolution of 1.83 A; (c) the study of the recently identified arene-binding site of GCPII through mutagenesis (Arg463Leu, Arg511Leu and Trp541Ala), inhibitor binding and enzyme kinetics with polyglutamylated folates as substrates; and (d) a comparison of the thermal stabilities and folate-hydrolyzing activities of GCPII wild-type and His475Tyr variants. As a result, the crystallographic data reveal considerable details about the binding mode of polyglutamylated folates to GCPII, especially the engagement of the arene binding site in recognizing the folic acid moiety. Additionally, the combined structural and kinetic data suggest that GCPII wild-type and His475Tyr variant are functionally identical. DATABASE: Structural data have been deposited in the RCSB Protein Data Bank database under accession numbers 4MCS (GCPII-His475Tyr-glutamate), 4MCP (GCPII-Glu424Ala-FolGlu1 ), 4MCQ (GCPII-Glu424Ala-FolGlu2 ) and 4MCR (GCPII-Glu424Ala-FolGlu3 ).

Structural and biochemical characterization of the folyl-poly-gamma-l-glutamate hydrolyzing activity of human glutamate carboxypeptidase II.,Navratil M, Ptacek J, Sacha P, Starkova J, Lubkowski J, Barinka C, Konvalinka J FEBS J. 2014 May 25. doi: 10.1111/febs.12857. PMID:24863754^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Navratil M, Ptacek J, Sacha P, Starkova J, Lubkowski J, Barinka C, Konvalinka J. Structural and biochemical characterization of the folyl-poly-gamma-l-glutamate hydrolyzing activity of human glutamate carboxypeptidase II. FEBS J. 2014 May 25. doi: 10.1111/febs.12857. PMID:24863754 doi:http://dx.doi.org/10.1111/febs.12857

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4mcp"

@@ Line 1: / Line 1: @@
 ==A high resolution structure of human glutamate carboxypeptidase II (GCPII) in complex with folyl-gamma-L-glutamic acid (pteroyldi-gamma-L-glutamic acid)==
 <StructureSection load='4mcp' size='340' side='right' caption='[[4mcp]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4mcq|4mcq]], [[4mcr|4mcr]], [[4mcs|4mcs]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mcp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mcp RCSB], [http://www.ebi.ac.uk/pdbsum/4mcp PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mcp OCA], [http://pdbe.org/4mcp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mcp RCSB], [http://www.ebi.ac.uk/pdbsum/4mcp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mcp ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4mcp" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Carboxypeptidase|Carboxypeptidase]]
 == References ==
 <references/>

4mcp

From Proteopedia

Revision as of 11:58, 5 August 2016

A high resolution structure of human glutamate carboxypeptidase II (GCPII) in complex with folyl-gamma-L-glutamic acid (pteroyldi-gamma-L-glutamic acid)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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