Difference between revisions of "Part:BBa K404111"

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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 />
 
<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 />
 
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https://static.igem.org/mediawiki/parts/a/a8/Freiburg10_GuanylateKinase.png <b>Figure 1: </b>Crystal structure (Sekulic et al. 2002)  of mouse guanylate kinase in complex with GMP and ADP (PDB: 1LVG).
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<b> Figure 1: </b>Crystal structure (Sekulic et al. 2002)  of mouse guanylate kinase in complex with GMP and ADP (PDB: 1LVG).
 
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Revision as of 21:52, 22 October 2010

Mouse guanylate kinase (mGMK)

Guanylate kinase (mGMK)
Freiburg10 VectorplasmidBricks 8.png
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

Freiburg10 VectorplasmidBricks 8.png


Sequence and Features


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    COMPATIBLE WITH RFC[21]
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    COMPATIBLE WITH RFC[25]
  • 1000
    INCOMPATIBLE WITH RFC[1000]
    Illegal SapI.rc site found at 45