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''Drosophila melanogaster'' glutaminyl cyclase (DromeQC but also known as CG10487 CG32412 or Dmel\CG32412) is a globular protein part of the α/β-hydrolase superfamily. DromeQC is an aminoacyltransferase (EC 2.3.2.5) that acts on N-terminal glutamine or glutamate residues, producing a stable cap resistant to protease degradation. The human orthologue of DromeQC (hQC) has been implicated in stabilizing amyloid Aβ peptides involved in neurodegenerative disorders such as Alzheimers<ref name="schilling">PMID: 18836460</ref>. It has been shown that DromeQC has a similar overall fold to hQC, as well as a conserved active site<ref name="main">PMID: 22897232</ref>. Thus DromeQC is an attractive candidate for transgenic models and mechanistic studies. | ''Drosophila melanogaster'' glutaminyl cyclase (DromeQC but also known as CG10487 CG32412 or Dmel\CG32412) is a globular protein part of the α/β-hydrolase superfamily. DromeQC is an aminoacyltransferase (EC 2.3.2.5) that acts on N-terminal glutamine or glutamate residues, producing a stable cap resistant to protease degradation. The human orthologue of DromeQC (hQC) has been implicated in stabilizing amyloid Aβ peptides involved in neurodegenerative disorders such as Alzheimers<ref name="schilling">PMID: 18836460</ref>. It has been shown that DromeQC has a similar overall fold to hQC, as well as a conserved active site<ref name="main">PMID: 22897232</ref>. Thus DromeQC is an attractive candidate for transgenic models and mechanistic studies. | ||
===Gene->Protein=== | ===Gene->Protein=== | ||
| - | DromeQC is encoded by chromosome 3, locus 64F4-64F5 in the ''D. melanogaster'' genome. It is transcribed into a 1622 nucleotide transcript containing | + | DromeQC is encoded by chromosome 3, locus 64F4-64F5 in the ''D. melanogaster'' genome. It is transcribed into a 1622 nucleotide transcript, containing 5' (36 nucleotides) and 3' (83 nucleotides) untranslated regions <ref>DromeQC Gene Card. NCBI. [http://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=Graphics&list_uids=38663]</ref>. The translated protein contains 340 residues corresponding to a M=38,028 Da. It contains a 27 residue signal sequence, suggesting its involvement in the secretory pathway <ref name="schilling"/>. |
==Structure== | ==Structure== | ||
[[Image:Overall structure.jpg|thumb|800px|Figure 1. A 3D graphical representation displaying the homodimer glutaminyl cyclase from ''Drosophila melanogaster'' (PDB: 4F9U). Secondary structure is depicted by red (α-helix) and yellow (β-strand) ribbons, glycosyl groups are coloured pinks, while hydrogen bonds between the two monomers are shown by dotted green lines. The active site of QC contains a chelated zinc ion represented by a gray sphere. Also bound to the active site of this crystal structure and depicted as blue is the inhibitor 1-(3,4-dimethoxyphenyl)-3-[3-(1H-imidazol-1-yl)propyl]thiourea.]] | [[Image:Overall structure.jpg|thumb|800px|Figure 1. A 3D graphical representation displaying the homodimer glutaminyl cyclase from ''Drosophila melanogaster'' (PDB: 4F9U). Secondary structure is depicted by red (α-helix) and yellow (β-strand) ribbons, glycosyl groups are coloured pinks, while hydrogen bonds between the two monomers are shown by dotted green lines. The active site of QC contains a chelated zinc ion represented by a gray sphere. Also bound to the active site of this crystal structure and depicted as blue is the inhibitor 1-(3,4-dimethoxyphenyl)-3-[3-(1H-imidazol-1-yl)propyl]thiourea.]] | ||
Revision as of 19:41, 30 March 2014
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Contents |
Introduction
Drosophila melanogaster glutaminyl cyclase (DromeQC but also known as CG10487 CG32412 or Dmel\CG32412) is a globular protein part of the α/β-hydrolase superfamily. DromeQC is an aminoacyltransferase (EC 2.3.2.5) that acts on N-terminal glutamine or glutamate residues, producing a stable cap resistant to protease degradation. The human orthologue of DromeQC (hQC) has been implicated in stabilizing amyloid Aβ peptides involved in neurodegenerative disorders such as Alzheimers[1]. It has been shown that DromeQC has a similar overall fold to hQC, as well as a conserved active site[2]. Thus DromeQC is an attractive candidate for transgenic models and mechanistic studies.
Gene->Protein
DromeQC is encoded by chromosome 3, locus 64F4-64F5 in the D. melanogaster genome. It is transcribed into a 1622 nucleotide transcript, containing 5' (36 nucleotides) and 3' (83 nucleotides) untranslated regions [3]. The translated protein contains 340 residues corresponding to a M=38,028 Da. It contains a 27 residue signal sequence, suggesting its involvement in the secretory pathway [1].
Structure
Image:Overall structure.jpg
Figure 1. A 3D graphical representation displaying the homodimer glutaminyl cyclase from Drosophila melanogaster (PDB: 4F9U). Secondary structure is depicted by red (α-helix) and yellow (β-strand) ribbons, glycosyl groups are coloured pinks, while hydrogen bonds between the two monomers are shown by dotted green lines. The active site of QC contains a chelated zinc ion represented by a gray sphere. Also bound to the active site of this crystal structure and depicted as blue is the inhibitor 1-(3,4-dimethoxyphenyl)-3-[3-(1H-imidazol-1-yl)propyl]thiourea.
References
- ↑ 1.0 1.1 Schilling S, Zeitschel U, Hoffmann T, Heiser U, Francke M, Kehlen A, Holzer M, Hutter-Paier B, Prokesch M, Windisch M, Jagla W, Schlenzig D, Lindner C, Rudolph T, Reuter G, Cynis H, Montag D, Demuth HU, Rossner S. Glutaminyl cyclase inhibition attenuates pyroglutamate Abeta and Alzheimer's disease-like pathology. Nat Med. 2008 Oct;14(10):1106-11. doi: 10.1038/nm.1872. Epub 2008 Sep 28. PMID:18836460 doi:http://dx.doi.org/10.1038/nm.1872
- ↑ Koch B, Kolenko P, Buchholz M, Ruiz Carrillo D, Parthier C, Wermann M, Rahfeld JU, Reuter G, Schilling S, Stubbs MT, Demuth HU. Crystal Structures of Glutaminyl Cyclases from Drosophila melanogaster Reveal Active Site Conservation between Insect and Mammalian QCs. Biochemistry. 2012 Aug 16. PMID:22897232 doi:10.1021/bi300687g
- ↑ DromeQC Gene Card. NCBI. [1]
