Fpg Nei Protein Superfamily

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3cin, resolution 1.70Å ()
Ligands: , ,
Gene: TM1419, TM_1419 (Thermotoga maritima MSB8)
Activity: Inositol-3-phosphate synthase, with EC number 5.5.1.4
Resources: FirstGlance, OCA, RCSB, PDBsum, TOPSAN
Coordinates: save as pdb, mmCIF, xml



Contents

DNA Repair and Base Excision DNA Repair

For a video of DNA repair click here. The picture below also illustrates DNA repair: Image:DNARepair.png The genome of any living organisms is being continuously affected by exogenous and endogenous agents, such as ultraviolet light, ionizing radiation, different chemicals and the cell's own metabolites (such as reactive oxygen). Therefore, different systems have evolved to repair these damages. With some of these systems shared throughout all lifeforms. Therefore, the proper functioning of DNA repair is critical for survival. There are six pathways of DNA repair (reviewed in Friedberg et al), and one of the is base-excision repair. The latter's distinguishing feature is that it removes lesions as single bases, as opposed to dNMPs or short oligonucleotides like other systems. [1]

Base excision repair's signature enzyme are the DNA glycosylases. These enzymes work by recognizing and removing a single damaged base from DNA. They are called DNA glycosylases because they hydrolize the N-glycosidic bond of the damaged deoxynucleoside. The subsequent steps of the pathway (strand incision, gap-filling and ligation) are done by other enzymes. See below for a cartoon of the process [2][3]:

Evolution and related structures

Cartoon phylogenetic tree of the FpgNei protein family.  Neil1 is one among several metazoan repair proteins
Cartoon phylogenetic tree of the FpgNei protein family. Neil1 is one among several metazoan repair proteins
Neil1 is part of the FpgNei superfamily of base excision repair proteins. And its one of 3 DNA glycosylases present in vertebrates, and in humans in particular. The evolution of this superfamily is not totally clear.

Homologous structures have been solved, including Fpg protein from Lactococcus Lactis (1pjj)[4], Bacillus Stereothermophilus (1r2y)[5], Thermos Thermophilus (1ee8)[6] and Escherichia Coli(1k82)[7] and Nei from Escherichia Coli (1k3w)[8]. The overall structure is similar, and some of the damages include 8-oxoguanine and fapyG (1xc8)[9].

3D structures of Fpg and Nei

DNA glycosylase

Additional Resources

For additional information, see: DNA Replication, Repair, and Recombination
For additional information, see: Nucleic Acids

References

  1. Zharkov DO. Base excision DNA repair. Cell Mol Life Sci. 2008 May;65(10):1544-65. PMID:18259689 doi:10.1007/s00018-008-7543-2
  2. Zharkov DO. Base excision DNA repair. Cell Mol Life Sci. 2008 May;65(10):1544-65. PMID:18259689 doi:10.1007/s00018-008-7543-2
  3. Robertson AB, Klungland A, Rognes T, Leiros I. DNA repair in mammalian cells: Base excision repair: the long and short of it. Cell Mol Life Sci. 2009 Mar;66(6):981-93. PMID:19153658 doi:10.1007/s00018-009-8736-z
  4. Pereira de Jesus K, Serre L, Zelwer C, Castaing B. Structural insights into abasic site for Fpg specific binding and catalysis: comparative high-resolution crystallographic studies of Fpg bound to various models of abasic site analogues-containing DNA. Nucleic Acids Res. 2005 Oct 20;33(18):5936-44. Print 2005. PMID:16243784 doi:http://dx.doi.org/33/18/5936
  5. Fromme JC, Verdine GL. DNA lesion recognition by the bacterial repair enzyme MutM. J Biol Chem. 2003 Dec 19;278(51):51543-8. Epub 2003 Oct 1. PMID:14525999 doi:10.1074/jbc.M307768200
  6. Sugahara M, Mikawa T, Kumasaka T, Yamamoto M, Kato R, Fukuyama K, Inoue Y, Kuramitsu S. Crystal structure of a repair enzyme of oxidatively damaged DNA, MutM (Fpg), from an extreme thermophile, Thermus thermophilus HB8. EMBO J. 2000 Aug 1;19(15):3857-69. PMID:10921868 doi:http://dx.doi.org/10.1093/emboj/19.15.3857
  7. Gilboa R, Zharkov DO, Golan G, Fernandes AS, Gerchman SE, Matz E, Kycia JH, Grollman AP, Shoham G. Structure of formamidopyrimidine-DNA glycosylase covalently complexed to DNA. J Biol Chem. 2002 May 31;277(22):19811-6. Epub 2002 Mar 23. PMID:11912217 doi:http://dx.doi.org/10.1074/jbc.M202058200
  8. Zharkov DO, Golan G, Gilboa R, Fernandes AS, Gerchman SE, Kycia JH, Rieger RA, Grollman AP, Shoham G. Structural analysis of an Escherichia coli endonuclease VIII covalent reaction intermediate. EMBO J. 2002 Feb 15;21(4):789-800. PMID:11847126 doi:10.1093/emboj/21.4.789
  9. Coste F, Ober M, Carell T, Boiteux S, Zelwer C, Castaing B. Structural basis for the recognition of the FapydG lesion (2,6-diamino-4-hydroxy-5-formamidopyrimidine) by formamidopyrimidine-DNA glycosylase. J Biol Chem. 2004 Oct 15;279(42):44074-83. Epub 2004 Jul 10. PMID:15249553 doi:10.1074/jbc.M405928200

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