Difference between revisions of "Part:BBa K404111"

Latest revision as of 22:07, 22 October 2010

Mouse guanylate kinase (mGMK)

Guanylate kinase (mGMK)

BioBrick Nr.	K404111 BBa K404111
RFC standard	RFC 25
Requirement	pSB1C3
Source	synthetic
Submitted by	[http://2010.igem.org/Team:Freiburg_Bioware FreiGEM 2010]

Guanylate kinases (GMKs) are involved in the salvage pathway of mono-phosphorylated guanosine (GMP) nucleosides to GDP therefore being essential in nucleotide maturation (Stolworthy & Black 2001). By introducing transgenic thymidine kinases (TKs) into tumor cells, a bottleneck occurs by overexpression of mono-phosphorylated intermediates. To overcome the accumulation of these non-toxic molecules, Willmon, Krabbenhoft, & Black (2006) fused the herpes simplex virus thymidine kinase (HSV-TK) to the guanylate kinase from M. musculus and demonstrated enhanced tumor killing in vitro.

Figure 1: Crystal structure (Sekulic et al. 2002) of mouse guanylate kinase in complex with GMP and ADP (PDB: 1LVG).

The iGEM team Freiburg_Bioware provides the mGMK BioBrick part within the ‘Virus Construction Kit’ for therapeutical applications. Producing viral particles with encapsidated single-stranded DNA containing the fusion gene mGMK_TK enhances the efficacy of the prodrug-activating system leading to cell death of targeted tumor cells

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 <partinfo>BBa_K404111 short</partinfo>
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 {| style="color:black" cellpadding="6" cellspacing="1" border="2" align="right"
-! colspan="2" style="background:#66bbff;"|https://parts.igem.org/Part:BBa_K404111
+! colspan="2" style="background:#66bbff;"|[https://parts.igem.org/Part:BBa_K404111 Guanylate kinase (mGMK)]
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 ! colspan="2"|[[image:Freiburg10 VectorplasmidBricks 8.png|200px]]
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 <b>Guanylate kinases  (GMKs)</b> are involved in the salvage pathway of <b>mono-phosphorylated guanosine (GMP) </b>nucleosides to GDP therefore being essential in nucleotide maturation (Stolworthy & Black 2001). By introducing transgenic thymidine kinases (TKs) into tumor cells, a bottleneck occurs by overexpression of mono-phosphorylated intermediates. To overcome the accumulation of these non-toxic molecules, Willmon, Krabbenhoft, & Black (2006) fused the herpes simplex virus thymidine kinase (HSV-TK) to the guanylate kinase from M. musculus and demonstrated enhanced tumor killing in vitro. <br />
 <br />
-The <b>iGEM team Freiburg_Bioware</b> provides the mGMK BioBrick part within the <b>‘Virus Construction Kit’</b> for therapeutical applications. Producing viral particles with encapsidated single-stranded DNA containing the fusion gene mGMK_TK enhances the efficacy of the prodrug-activating system leading to cell death of targeted tumor cells
+<html>
+<img src="https://static.igem.org/mediawiki/parts/a/a8/Freiburg10_GuanylateKinase.png" style="margin: 0px 30px 0px 0px;" />
+ <b> Figure 1: </b>Crystal structure (Sekulic et al. 2002)  of mouse guanylate kinase in complex with GMP and ADP (PDB: 1LVG).
+<br />
+<br />
+<br />
+The <b>iGEM team Freiburg_Bioware</b> provides the mGMK BioBrick part within the <b>‘Virus Construction Kit’</b> for therapeutical applications. Producing viral particles with encapsidated single-stranded DNA containing the fusion gene mGMK_TK enhances the efficacy of the prodrug-activating system leading to cell death of targeted tumor cells
 </p>
+<br />
+</div></html>
+[[Image:Freiburg10_VectorplasmidBricks 8.png|thumb|center|480px]]<br>
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 <partinfo>BBa_K404111 parameters</partinfo>
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+<html>
+<h3>References</h3>
+<b>Sekulic, N. et al.</b>, 2002. Structural characterization of the closed conformation of mouse guanylate kinase. The Journal of biological chemistry, 277(33), 30236-43. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12036965.
+<br />
+<b>Stolworthy, T.S. & Black, M.E.</b>, 2001. The mouse guanylate kinase double mutant E72Q/D103N is a functional adenylate kinase. Protein engineering, 14(11), 903-9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11742110.
+<br />
+<b>Willmon, C.L., Krabbenhoft, E. & Black, M.E.</b>, 2006. A guanylate kinase/HSV-1 thymidine kinase fusion protein enhances prodrug-mediated cell killing. Gene therapy, 13(17), 1309-12. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16810197.
+</html>