Deaminase

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<StructureSection load='1aln' size='350' side='right' caption='Structure of cytidine deaminase complex with deazacytosine (PDB entry [[1aln]])' scene=''>
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<StructureSection load='1p6o' size='350' side='right' caption='Structure of yeast cytosine deaminase complex with pyrimidine-based inhibitor, acetate, Ca+2 (green) and Zn+2 (grey) ions (PDB entry [[1p6o]])' scene='55/551217/Cv/1'>
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__TOC__
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== Function ==
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'''Deaminase''' removes an amine group from a molecule. '''Cytosine deaminase''' (CDDA) converts cytosine to uracil. '''Cytidine deaminase''' (CDDA) converts cytidine to uridine. 5-methylcytosine deaminase (MCDA) produces thymine. '''Guanine deaminase''' (GDA) converts guanine to xanthine. '''Adenine deaminase''' (ADA) converts adenine to hypoxanthine.
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'''Deaminase''' removes an amine group from an amino acid and the rest of the molecule is recycled. <br />
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* '''Cytosine deaminase''' (CDA) converts cytosine to uracil. <br />
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* '''Cytidine deaminase''' (CDDA) converts cytidine to uridine. <ref>PMID:12651944</ref> <br />
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* '''5-methylcytosine deaminase''' (MCDA) produces thymine. <br />
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* '''Guanine deaminase''' (GDA) converts guanine to xanthine. <ref>PMID:22662200</ref><br />
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* '''Adenine deaminase''' (ADA) converts adenine to hypoxanthine.<br />
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* '''Glucosamine 6-phosphate deaminase''' (GPD) converts glucosamine 6-phosphate to fructose 6-phosphate.<br />
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* '''1-aminocyclopropane-1-carboxylate deaminase''' (ACCD) converts 1-aminocyclopropane-1-carboxylic acid to 2-oxobutyrate.<br />
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* '''dCTP deaminase''' (ADA) converts dCTP to dUTP.<br />
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* '''dCTP deaminase-dUTPase''' (DCD-DUT) converts dCTP to dUMP.<br />
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* '''Blasticidin-S deaminase''' (BSD) converts blasticidin-S to deaminohydroxyblasticidin.<br />
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* '''Threonine deaminase''' (THD) converts L-threonine to α-ketobutyrate.<br />
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* '''L-serine deaminase''' (LSD) converts L-serine to pyruvate.<br />
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* '''D-serine deaminase''' (DSD) converts D-serine to pyruvate.<br />
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* '''Aminofutalosine deaminase''' deaminates aminofutalosine which is an intermediate in the menaquinone biosynthesis in ''Helicobacter pylori'' <ref>PMID:34077175</ref>. <br />
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== 3D Structures of deaminase ==
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== Relevance ==
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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Cytosine deaminase is used in cancer therapy. After treatment by 5-fluorouracil, the cytosine deaminase gene is introduced to the tumor resulting in intratumor chemotherapy. <ref>PMID:17938268</ref>
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'''Cytidine deaminase'''
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== Disease ==
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[[1r5t]] – yCDA - yeast <BR />
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Mutation in adenine deaminase results in deficiency of the enzyme and is the cause of severe combined immunodeficiency (SCID).
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[[2a8n]] – AtCDA – ''Agrobacterium tumefaciens'' <BR />
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[[2g84]] – CDA – ''Nitrosomonas europaea'' <BR />
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[[2d30]] – CDA – ''Bacillus anthracis'' <BR />
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[[3dmo]] – CDA – ''Burkholderia pseudomallei'' <BR />
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[[3ijf]] – CDA – ''Mycobacterium tuberculosis'' <BR />
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[[3mpz]] – CDA – ''Mycobacterium smegmatis'' <BR />
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[[3r2n]] – CDA – ''Mycobacterium leprae'' <BR />
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[[4f3w]] – CDA – ''Mycobacterium marinum'' <BR />
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''Cytidine deaminase complex with nucleoside''
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== Structural highlights ==
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[[1ctt]] – EcCDA + dihydro-pyrimidinone – ''Escherichia coli'' <BR />
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The <scene name='55/551217/Cv/3'>active site of cytosine deaminase contains a catalytically active zinc</scene> atom.<ref>PMID:12906827</ref>
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[[1ctu]] – EcCDA + hydroxyl-dihydro-zebularine <BR />
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[[1af2]] – EcCDA + uridine <BR />
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[[1aln]] – EcCDA + deazacytidine <BR />
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[[1jtk]] – BsCDA + tetrahydrodeoxyuridine - ''Bacillus subtilis'' <BR />
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[[1uwz]], [[1ux0]], [[1ux1]] – BsCDA (mutant) + tetrahydrodeoxyuridine <BR />
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[[1mq0]] – hCDA + β-ribofuranosyl diazepinone - human <BR />
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[[1zab]] – mCDA + deazauridine - mouse <BR />
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[[2fr5]] – mCDA + tetrahydrouridine <BR />
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[[2fr6]] – mCDA + cytidine + uridine <BR />
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[[4eg2]] – CDA + uridine - ''Vibrio cholerae'' <BR />
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'''Cytosine deaminase'''
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== 3D Structures of deaminase ==
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[[Deaminase 3D structures]]
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[[1k6w]] – EcCDDA <BR />
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[[1r9x]], [[1r9y]], [[1r9z]], [[1ra0]], [[1ra5]], [[3g77]] – EcCDDA (mutant)<BR />
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[[1rb7]], [[1uaq]] – yCDDA <BR />
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[[1ysb]], [[1ysd]] – yCDDA (mutant)<BR />
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''Cytosine deaminase complex''
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[[3r0d]] – EcCDDA + Zn <BR />
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[[3rn6]] – EcCDDA + Zn + iso-guanine<BR />
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[[1k70]] – EcCDDA + pyrimidine derivative<BR />
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[[1rak]] – EcCDDA (mutant) + pyrimidine derivative<BR />
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[[3o7u]] – EcCDDA + Zn + phosphono-cytosine<BR />
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[[1ox7]] – yCDDA + Zn <BR />
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[[1p6o]] – yCDDA + pyrimidine derivative<BR />
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[[2o3k]] – yCDDA (mutant) + pyrimidine derivative<BR />
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'''Guanine deaminase'''
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[[1tiy]], [[1wkq]] – BsGDA <BR />
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[[3e0l]] – hGDA<br />
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''Guanine deaminase complex with nucleoside''
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[[2i9u]] – GDA + guanine – ''Clostridium acetobutylicum'' <BR />
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[[2ood]] – GDA + guanine – ''Bradrhizobium japonicum'' <BR />
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[[2uz9]] – hGDA + xanthine <BR />
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[[4aql]] – hGDA + valacyclovir <BR />
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'''Adenine deaminase'''
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[[2ics]] – ADA - ''Enterococcus faecalis''<BR />
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[[3nqb]], [[3t81]], [[3t8l]] – AtADA <BR />
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'''Adenosine deaminase'''
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</StructureSection>
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See [[Adenosine deaminase]]
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== References ==
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Structure of yeast cytosine deaminase complex with pyrimidine-based inhibitor, acetate, Ca+2 (green) and Zn+2 (grey) ions (PDB entry 1p6o)

Drag the structure with the mouse to rotate

References

  1. ↑ Bransteitter R, Pham P, Scharff MD, Goodman MF. Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4102-7. Epub 2003 Mar 21. PMID:12651944 doi:http://dx.doi.org/10.1073/pnas.0730835100
  2. ↑ Egeblad L, Welin M, Flodin S, Graslund S, Wang L, Balzarini J, Eriksson S, Nordlund P. Pan-Pathway Based Interaction Profiling of FDA-Approved Nucleoside and Nucleobase Analogs with Enzymes of the Human Nucleotide Metabolism. PLoS One. 2012;7(5):e37724. Epub 2012 May 25. PMID:22662200 doi:10.1371/journal.pone.0037724
  3. ↑ Feng M, Harijan RK, Harris LD, Tyler PC, Frohlich RFG, Brown M, Schramm VL. Aminofutalosine Deaminase in the Menaquinone Pathway of Helicobacter pylori. Biochemistry. 2021 Jun 22;60(24):1933-1946. doi: 10.1021/acs.biochem.1c00215., Epub 2021 Jun 2. PMID:34077175 doi:http://dx.doi.org/10.1021/acs.biochem.1c00215
  4. ↑ Negroni L, Samson M, Guigonis JM, Rossi B, Pierrefite-Carle V, Baudoin C. Treatment of colon cancer cells using the cytosine deaminase/5-fluorocytosine suicide system induces apoptosis, modulation of the proteome, and Hsp90beta phosphorylation. Mol Cancer Ther. 2007 Oct;6(10):2747-56. PMID:17938268 doi:http://dx.doi.org/10.1158/1535-7163.MCT-07-0040
  5. ↑ Ireton GC, Black ME, Stoddard BL. The 1.14 A crystal structure of yeast cytosine deaminase: evolution of nucleotide salvage enzymes and implications for genetic chemotherapy. Structure. 2003 Aug;11(8):961-72. PMID:12906827

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Michal Harel, Alexander Berchansky

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