User:Alexander Rudecki/Sandbox 1: Difference between revisions

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==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<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; also known as CG10487, CG32412 or Dmel\CG32412) is a globular protein part of the α/β-hydrolase superfamily<ref name="main">PMID: 22897232</ref>. DromeQC is an aminoacyltransferase (EC 2.3.2.5) that acts on N-terminal glutamine or glutamate residues, producing a protease-resistant cap in substrate proteins<ref name="main"/>. 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"/>. Thus, DromeQC is an attractive candidate for transgenic models and mechanistic studies, which may further characterize neurodegenerative disorders and help develop treatments.

===DNA--> RNA--> Protein===

DromeQC is encoded by chromosome 3L, locus 64F4-64F5 in the ''D. melanogaster'' genome<ref name="genecard">DromeQC Gene Card. NCBI. [http://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=Graphics&list_uids=38663]</ref>. It is transcribed into a 1622 nucleotide transcript, containing 5' (36 nucleotides) and 3' (83 nucleotides) untranslated regions <ref name="genecard"/>. The translated protein contains 340 residues corresponding to a M=38,028 Da<ref>DromeQC. UniProt. [http://www.uniprot.org/uniprot/Q9VRQ9]</ref>. It contains a 27 residue signal sequence, suggesting its involvement in the secretory pathway <ref name="schilling"/>.

DromeQC is encoded by chromosome 3L, locus 64F4-64F5 in the ''D. melanogaster'' genome<ref name="genecard">DromeQC Gene Card. NCBI. [http://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=Graphics&list_uids=38663]</ref>. This gene is transcribed into a 1622 nucleotide transcript, containing 5' (36 nucleotides) and 3' (83 nucleotides) untranslated regions <ref name="genecard"/>. The translated protein contains 340 residues corresponding to a mass of 38,028 Da<ref>DromeQC. UniProt. [http://www.uniprot.org/uniprot/Q9VRQ9]</ref>. It also contains a 27 residue signal sequence, suggesting its involvement in the secretory pathway <ref name="schilling"/>.

===Protein Family===

DromeQC belongs to the α/β-hydrolase fold superfamily; this superfamily exhibits a β-sheet core (5-8 strands) connected to α helices forming an α/β/α sandwhich<ref name="family">PMID: 23193256</ref>. ~~As of present,~~ the ESTHER database (ESTerases and α/β-Hydrolase Enzymes and Relatives) contains 168 protein families<ref>Lenfant, N., Hotelier, T., Velluet, E., Bourne, Y., Marchot, P., and A Chatonnet. (2013) ESTHER, the database of the alpha/beta-hydrolase fold superfamily of proteins: tools to explore diversity of functions. Nucleic Acids Research 41: D423-9. [http://bioweb.ensam.inra.fr/ESTHER/general?what=index]</ref>. Most of the proteins in this superfamily function via a conserved catalytic triad - a nucleophile, acid and base - ~~with the residues~~ present on the loops of the active site<ref name="family"/>. Further information on catalysis is found in the 'Catalytic Mechanism' section on this page.

DromeQC belongs to the α/β-hydrolase fold superfamily; this superfamily exhibits a β-sheet core (5-8 strands) connected to α-helices, forming an α/β/α sandwhich<ref name="family">PMID: 23193256</ref>. The α/β-hydrolases are well characterized in the ESTHER database (ESTerases and α/β-Hydrolase Enzymes and Relatives), which as of present contains 168 protein families<ref>Lenfant, N., Hotelier, T., Velluet, E., Bourne, Y., Marchot, P., and A Chatonnet. (2013) ESTHER, the database of the alpha/beta-hydrolase fold superfamily of proteins: tools to explore diversity of functions. Nucleic Acids Research 41: D423-9. [http://bioweb.ensam.inra.fr/ESTHER/general?what=index]</ref>. Most of the proteins in this superfamily function via a conserved catalytic triad - a nucleophile, acid and base - which is present on the loops of the active site<ref name="family"/>. Further information on catalysis is found in the 'Catalytic Mechanism' section on this page.

It is interesting that DromeQC prevents protein degradation from aminopeptidases, yet theses two enzymes share a common fold and active site ~~residues~~<ref>PMID: 15028118</ref>. This suggests that the enzymes act in a similar manner, with ~~contrasting~~ effects on substrate.

It is interesting that DromeQC prevents protein degradation from aminopeptidases, yet theses two enzymes share a common fold and active site<ref>PMID: 15028118</ref>. This suggests that the enzymes act in a similar manner, with opposing effects on substrate.

==Structure==

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 ==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<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; also known as CG10487, CG32412 or Dmel\CG32412) is a globular protein part of the α/β-hydrolase superfamily<ref name="main">PMID: 22897232</ref>. DromeQC is an aminoacyltransferase (EC 2.3.2.5) that acts on N-terminal glutamine or glutamate residues, producing a protease-resistant cap in substrate proteins<ref name="main"/>. 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"/>. Thus, DromeQC is an attractive candidate for transgenic models and mechanistic studies, which may further characterize neurodegenerative disorders and help develop treatments.
 ===DNA--> RNA--> Protein===
-DromeQC is encoded by chromosome 3L, locus 64F4-64F5 in the ''D. melanogaster'' genome<ref name="genecard">DromeQC Gene Card. NCBI. [http://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=Graphics&list_uids=38663]</ref>. It is transcribed into a 1622 nucleotide transcript, containing 5' (36 nucleotides) and 3' (83 nucleotides) untranslated regions <ref name="genecard"/>. The translated protein contains 340 residues corresponding to a M=38,028 Da<ref>DromeQC. UniProt. [http://www.uniprot.org/uniprot/Q9VRQ9]</ref>. It contains a 27 residue signal sequence, suggesting its involvement in the secretory pathway <ref name="schilling"/>.
+DromeQC is encoded by chromosome 3L, locus 64F4-64F5 in the ''D. melanogaster'' genome<ref name="genecard">DromeQC Gene Card. NCBI. [http://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=Graphics&list_uids=38663]</ref>. This gene is transcribed into a 1622 nucleotide transcript, containing 5' (36 nucleotides) and 3' (83 nucleotides) untranslated regions <ref name="genecard"/>. The translated protein contains 340 residues corresponding to a mass of 38,028 Da<ref>DromeQC. UniProt. [http://www.uniprot.org/uniprot/Q9VRQ9]</ref>. It also contains a 27 residue signal sequence, suggesting its involvement in the secretory pathway <ref name="schilling"/>.
 ===Protein Family===
-DromeQC belongs to the α/β-hydrolase fold superfamily; this superfamily exhibits a β-sheet core (5-8 strands) connected to α helices forming an α/β/α sandwhich<ref name="family">PMID: 23193256</ref>. As of present, the ESTHER database (ESTerases and α/β-Hydrolase Enzymes and Relatives) contains 168 protein families<ref>Lenfant, N., Hotelier, T., Velluet, E., Bourne, Y., Marchot, P., and A Chatonnet. (2013) ESTHER, the database of the alpha/beta-hydrolase fold superfamily of proteins: tools to explore diversity of functions. Nucleic Acids Research 41: D423-9. [http://bioweb.ensam.inra.fr/ESTHER/general?what=index]</ref>. Most of the proteins in this superfamily function via a conserved catalytic triad - a nucleophile, acid and base - with the residues present on the loops of the active site<ref name="family"/>. Further information on catalysis is found in the 'Catalytic Mechanism' section on this page.
+DromeQC belongs to the α/β-hydrolase fold superfamily; this superfamily exhibits a β-sheet core (5-8 strands) connected to α-helices, forming an α/β/α sandwhich<ref name="family">PMID: 23193256</ref>. The α/β-hydrolases are well characterized in the ESTHER database (ESTerases and α/β-Hydrolase Enzymes and Relatives), which as of present contains 168 protein families<ref>Lenfant, N., Hotelier, T., Velluet, E., Bourne, Y., Marchot, P., and A Chatonnet. (2013) ESTHER, the database of the alpha/beta-hydrolase fold superfamily of proteins: tools to explore diversity of functions. Nucleic Acids Research 41: D423-9. [http://bioweb.ensam.inra.fr/ESTHER/general?what=index]</ref>. Most of the proteins in this superfamily function via a conserved catalytic triad - a nucleophile, acid and base - which is present on the loops of the active site<ref name="family"/>. Further information on catalysis is found in the 'Catalytic Mechanism' section on this page.
-It is interesting that DromeQC prevents protein degradation from aminopeptidases, yet theses two enzymes share a common fold and active site residues<ref>PMID: 15028118</ref>. This suggests that the enzymes act in a similar manner, with contrasting effects on substrate.
+It is interesting that DromeQC prevents protein degradation from aminopeptidases, yet theses two enzymes share a common fold and active site<ref>PMID: 15028118</ref>. This suggests that the enzymes act in a similar manner, with opposing effects on substrate.
 ==Structure==