2afx: Difference between revisions
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[[Image:2afx.gif|left|200px]] | [[Image:2afx.gif|left|200px]] | ||
'''Crystal structure of human glutaminyl cyclase in complex with 1-benzylimidazole''' | {{Structure | ||
|PDB= 2afx |SIZE=350|CAPTION= <scene name='initialview01'>2afx</scene>, resolution 1.64Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=1BN:1-BENZYL-1H-IMIDAZOLE'>1BN</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Glutaminyl-peptide_cyclotransferase Glutaminyl-peptide cyclotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.5 2.3.2.5] | |||
|GENE= QPCT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Crystal structure of human glutaminyl cyclase in complex with 1-benzylimidazole''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2AFX is a [ | 2AFX 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=2AFX OCA]. | ||
==Reference== | ==Reference== | ||
Crystal structures of human glutaminyl cyclase, an enzyme responsible for protein N-terminal pyroglutamate formation., Huang KF, Liu YL, Cheng WJ, Ko TP, Wang AH, Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13117-22. Epub 2005 Aug 31. PMID:[http:// | Crystal structures of human glutaminyl cyclase, an enzyme responsible for protein N-terminal pyroglutamate formation., Huang KF, Liu YL, Cheng WJ, Ko TP, Wang AH, Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13117-22. Epub 2005 Aug 31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16135565 16135565] | ||
[[Category: Glutaminyl-peptide cyclotransferase]] | [[Category: Glutaminyl-peptide cyclotransferase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: metalloprotein]] | [[Category: metalloprotein]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:49:12 2008'' | ||
Revision as of 16:49, 20 March 2008
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| , resolution 1.64Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | QPCT (Homo sapiens) | ||||||
| Activity: | Glutaminyl-peptide cyclotransferase, with EC number 2.3.2.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human glutaminyl cyclase in complex with 1-benzylimidazole
OverviewOverview
N-terminal pyroglutamate (pGlu) formation from its glutaminyl (or glutamyl) precursor is required in the maturation of numerous bioactive peptides. The aberrant formation of pGlu may be related to several pathological processes, such as osteoporosis and amyloidotic diseases. This N-terminal cyclization reaction, once thought to proceed spontaneously, is greatly facilitated by the enzyme glutaminyl cyclase (QC). To probe this important but poorly understood modification, we present here the structure of human QC in free form and bound to a substrate and three imidazole-derived inhibitors. The structure reveals an alpha/beta scaffold akin to that of two-zinc exopeptidases but with several insertions and deletions, particularly in the active-site region. The relatively closed active site displays alternate conformations due to the different indole orientations of Trp-207, resulting in two substrate (glutamine t-butyl ester)-binding modes. The single zinc ion in the active site is coordinated to three conserved residues and one water molecule, which is replaced by an imidazole nitrogen upon binding of the inhibitors. Together with structural and kinetic analyses of several active-site-mutant enzymes, a catalysis mechanism of the formation of protein N-terminal pGlu is proposed. Our results provide a structural basis for the rational design of inhibitors against QC-associated disorders.
About this StructureAbout this Structure
2AFX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of human glutaminyl cyclase, an enzyme responsible for protein N-terminal pyroglutamate formation., Huang KF, Liu YL, Cheng WJ, Ko TP, Wang AH, Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13117-22. Epub 2005 Aug 31. PMID:16135565
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