Superoxide dismutase active site

CL Eisher, J-L Chen, J Li, D Bashford, L Noodleman. Density-functional and electrostatic calculations for a model of a manganese superoxide dismutase active site in aqueous solution. J Phys Chem 100 13498-13505, 1996. 

Carloni, P., P. E. Blochl, and M. Parrinello. 1995. Electronic Structure of the Cu, Zn Superoxide Dismutase Active Site and Its Interactions with the Substrate. J. Phys. Chem. 99, 1338. 

Carloni, P., Blochl, P. E. and Parrinello, M. Electronic structure of the Cu,Zn superoxide dismutase active site and its interactions with the substrate, J.Phys.Chem., 99 (1995), 1338-1348... 

LoU, B., Kern, J., Saenger, W., Zouni, A. and Biesiadka, J. (2005) Towards complete cofactor arrangement in the 3.0 A resolution structure of photosystem II, Nature, 438, 1040-1044. Miller, A.-F. (2004) Superoxide dismutases active sites that save, but a protein that kills, Curr. Opin. Chem. Biol., 8, 162-168. 

Miller, A.-F. (2004). Superoxide dismutases active sites that save, but a protein that kills. Current Opinion in Chemical Biology, 8, 162—168. 

Szilagyi RK, Bryngelson PA et al (2004) S K-edge X-ray absorption spectroscopic investigation of the Ni-containing superoxide dismutase active site new structural insight into the mechanism. J Am Chem Soc 126 3018-3019... 

While the stoichiometries of the Mn SOD enzymes appear to vary, the properties of the Mn-binding site do not. This is borne out in the electronic spectra of these proteins, which display a great degree of similarity despite the diversity of sources from which they have been isolated (Table II). This type of spectrum is distinctive for manganese in the trivalent oxidation state (3). The native enzymes are EPR silent, as might be anticipated if they contained Mn solely as the trivalent ion (S = 2) (1, 6,12,18-20, 24). However, when the enzymes are denatured, the characteristic six-line pattern of Mn(II) (I = 5/2) appears. Magnetic susceptibility studies with the E. coli SOD were consistent with the presence of a monomeric Mn(III) complex with a zero-field splitting of 1 to 2 cm-1 (4). The enzymes are additionally metal specific (however, see Refs. 36 and 37) metal reconstitution studies with E. coli and B. stearothermophilus revealed a strict requirement for Mn for superoxide dismutase activity (2, 22, 23). 

It needs to be pointed out that in case of paraquat resistance increases in glutathione reductase and superoxide dismutase levels do not alone adequately explain tolerance. Glutathione levels and superoxide dismutase activity was found even lower in a paraquat-resistant Conyza biotype (35). Compartroentalization appears to be an important factor since paraquat apparently was neither transported into the leaves of resistant biotypes (36) nor did it reach its site of action in the chloroplast (37,38). 

The Cu chelates using EDTA or serum albumin display no superoxide dismutase activity. It is very attractive to conclude that — as in the case of the catalatic action of Cu2+ — one or more Cu-coordination sites are fully accessible to water or the substrate. 

The enzymatic activity of the zinc-free protein is pH-dependent whereas native CUjZnjSOD is active over a wide pH-range (pH 5.0-9.5) Cu(II) in the zinc binding site gives little superoxide dismutase activity. This conclusion arises from the observation that AgjCUjSOD in which copper is in the zinc binding site, has almost no activity and that the Cu Cu enzyme has nearly the same activity as... 

Klapper, I., Hagstrom, R., Fine, R., Sharp, K., Honig, B. Focusing of electric fields in the active site of cu,zn superoxide dismutase. Proteins Struct. Pune. Genet. 1 (1986) 47-79. 

Wuerges J, J-W Lee, Y-I Yim, H-S Yrm, S-O Kang, KD Carugo (2004) Crystal structure of nickel-containing superoxide dismutase reveals another type of active site. Proc Natl Acad Sci USA 101 8569-8574. 

Superoxide dismutases (SODs) are a family of cytosolic metalloenzymes that specifically remove (reviewed by Omar etal., 1992). SOD distribution within the body is ubiquitous, being found in erythrocytes as well as most organs and cell types. Three distinct mammalian SOD forms exist CuZnSOD, MnSOD and extracellular SOD (EC-SOD). Their amino-acid sequences differ as well as the transition metals at their active sites. Rheumatoid synovial fluid contains low levels of SOD activity and hence little protection from ROM generated by infiltrating PMNs (Blake etcU., 1981). Furthermore, leucocytes from patients with RA are deficient in MnSOD, which might promote the extracellular leakage of O2 (Pasquier et al., 1984). 

Klapper I, Hagstrom R, Fine R, Sharp K, Honig B (1986) Focusing of Electric Fields in the Active Site of Cu-Zn Superoxide Dismutase Effects of Ionic Strength and Amino-Acid Modification. Proteins 1 47-59. 

Nickel is found in thiolate/sulflde environment in the [NiFe]-hydrogenases and in CODH/ACS.33 In addition, either a mononuclear Ni-thiolate site or a dinuclear cysteine-S bridged structure are assumed plausible for the new class of Ni-containing superoxide dismutases, NiSOD (A).34 [NiFe]-hydrogenase catalyzes the two-electron redox chemistry of dihydrogen. Several crystal structures of [NiFe]-hydrogenases have demonstrated that the active site of the enzyme consists of a heterodinuclear Ni—Fe unit bound to thiolate sulfurs of cysteine residues with a Ni—Fe distance below 3 A (4) 35-39 This heterodinuclear active site has been the target of extensive model studies, which are summarized in Section 6.3.4.12.5. 

Imidazoles are of interest as bridging ligands particularly with regard to mimics of the active site of Cu-Zn superoxide dismutase (SOD). Structures with imidazolate bridges have been... 

One last class of mononuclear non-haem iron enzyme that we have not yet considered, consists of the microbial superoxide dismutases with Fe(III) at their active site. The crystal structure of the E. coli enzyme shows a coordination geometry reminiscent of protocatechuate 3,4-dioxygenase, with four endogenous protein ligands, three His and one Asp residue, and one bound water molecule (Carlioz et ah, 1988). 

---