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Last modified: 10 December 1998

Endonuclease III
Iron-sulphur cluster Formal oxidation states
Fe4S4 image
[Fe4S4](SgammaCys)4
Active species:

[Fe4S4]+; [Fe4S4]2+; [Fe4S4]3+
Fe3S4 image
[Fe3S4](SgammaCys)3
Inactive species:

[Fe3S4]0; [Fe3S4]+

Endonuclease III (EC 4.2.99.18) is a DNA repair enzyme which removes a number of damaged pyrimidines from DNA via its glycosylase activity and also cleaves the phosphodiester backbone at apurinic / apyrimidinic sites via a ß­elimination mechanism [1]. The native enzyme contains a single [Fe4S4]2+ cluster. Upon treatment with ferricyanide, a fraction of the clusters is converted into the [Fe3S4] state [2].

The 3­D structure of E. coli endonuclease III has been determined [3], and has been shown to contain two all­alpha domains: a sequence­continuous, six­helix domain (residues 22-132) and a Greek­key, four­helix domain formed by one N­terminal and three C­terminal helices (residues 1-21 and 133-211) together with the [Fe4S4] cluster (see Figure 2ABK). The cluster is bound entirely within the C­terminal loop by four cysteine residues with a ligation pattern CX6CX2CX5C which is distinct from all other known Fe4S4 proteins: 

                          II  III
                        ,--C--C--.
                       /   \  /   \
                       |  [Fe4S4]  |
                       \   /  \   /
                        `-C.  .C-'
                          I|  |IV  
                           |  `---COO¯   
                  +H3N·····'
This structural motif is referred to as a [Fe4S4] cluster loop (FCL) [4]. Two DNA­binding motifs have been proposed, one at either end of the interdomain groove: the helix­hairpin­helix (HhH) and FCL motifs. The primary role of the iron-sulphur cluster appears to involve positioning conserved basic residues for interaction with the DNA phosphate backbone by forming the loop of the FCL motif [4].

Endonuclease III in enzyme databases

ENZYME LIGAND BRENDA Official name Alternative names
4.2.99.18
4.2.99.18
4.2.99.18
 DNA­(apurinic or apyrimidinic site) lyase AP lyase; AP endonuclease class I; endodeoxyribonuclease (apurinic or apyrimidinic); deoxyribonuclease (apurinic or apyrimidinic); E. coli endonuclease III; phage-T4 UV endonuclease; Micrococcus luteus UV endonuclease

Endonuclease III in motif databases

PRINTS ID PRINTS AC PROSITE/BLOCKS ID PROSITE AC BLOCKS AC
-
-
 ENDONUCLEASE_III_1
ENDONUCLEASE_III_2		 PS00764
PS01155		 BL00764

Endonuclease III in alignment databases

Protein Superfamily Pfam LPFC 3­D alignment
80741; endonuclease III
-
-

Endonuclease III in 3­D databases

Endonuclease III contains single cubane­like [Fe4S4] cluster (see Figure 2ABK).

PDB scop BSMRELI
Base		 Header MMS Abstract ¹
2abk 2abk 2abk 2abk Endonuclease III; Escherichia coli MMS93066

¹ Macromolecular Structures abstract. Full text is available to BioMedNet Members

References

  1. Tainer, J.A., Thayer, M.M. and Cunningham, R.P. (1995) DNA repair proteins. Curr. Opin. Struct. Biol. 5, 20-26.
  2. Cunningham, R.P., Asahara, H., Bank, J.F., Scholes, C.P., Salerno, J.C., Surerus, K., Münck, E., McCracken, J., Peisach, J. and Emptage, M.H. (1989) Endonuclease III is an iron-sulfur protein. Biochemistry 28, 4450-4455.
  3. Kuo, C.­F., Jr., McRee, D.E., Fisher, C.L., O'Handley, S.F., Cunningham, R.P. and Tainer, J.A. (1992) Atomic structure of the DNA repair [4Fe-4S] enzyme endonuclease III. Science 258, 434-440.
  4. Thayer, M.M., Ahern, H., Xing, D., Cunningham, R.P. and Tainer, J.A. (1995) Novel DNA binding motifs in the DNA repair enzyme endonuclease III crystal structure. EMBO J. 14, 4108-4120.
Bibliography on structural studies of endonuclease III