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. 2016 Oct;56(9-10):640-648.
doi: 10.1002/ijch.201600069. Epub 2016 Jul 29.

The Rise of Radicals in Bioinorganic Chemistry

Harry B Gray  1 , Jay R Winkler  1
Affiliations

The Rise of Radicals in Bioinorganic Chemistry

Harry B Gray et al. Isr J Chem. 2016 Oct.

Abstract

Prior to 1950, the consensus was that biological transformations occurred in two-electron steps, thereby avoiding the generation of free radicals. Dramatic advances in spectroscopy, biochemistry, and molecular biology have led to the realization that protein-based radicals participate in a vast array of vital biological mechanisms. Redox processes involving high-potential intermediates formed in reactions with O2 are particularly susceptible to radical formation. Clusters of tyrosine (Tyr) and tryptophan (Trp) residues have been found in many O2-reactive enzymes, raising the possibility that they play an antioxidant protective role. In blue copper proteins with plastocyanin-like domains, Tyr/Trp clusters are uncommon in the low-potential single-domain electron-transfer proteins and in the two-domain copper nitrite reductases. The two-domain muticopper oxidases, however, exhibit clusters of Tyr and Trp residues near the trinuclear copper active site where O2 is reduced. These clusters may play a protective role to ensure that reactive oxygen species are not liberated during O2 reduction.

Keywords: Electron transfer; radicals; tryptophan; tyrosine.

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Figures

Figure 1
Figure 1
Polypeptide ribbon diagrams of single-domain cupredoxins highlighting locations of the Cu center (spheres) and Tyr/Trp chains with 5-Å (red) and 7.5-Å (green) ET cutoff distances: (a) Synechococcus elongatus plastocyanin (PC) (PDB ID 1BXV);[48] (b) Ulva pertusa Pc (1IUZ);[49] (c) Ulva prolifera PC (7PCY);[50] (d) Synechocystis sp. PCC 6803 Pc (1PCS);[51] (e) Chlamydomonas reinhardtii Pc (2PLT);[52] (f) Silene latifolia Pc (1BYP);[53] (g) Populus nigra Pc-B (4DP6);[54] (h) Populus nigra Pc-A (4DPB);[54] (i) Spinacia oleracea Pc (1AG6);[55] (j) Adiantum capillus-veneris Pc (1KDJ);[56] (k) Nostoc sp. PCC 7120 Pc (2CJ3); (l) Phormidium laminosum Pc (2Q5B); (m) Anabaena variabilis Pc (2GIM);[57] (n) Paracoccus denitrificans amicyanin (Am) (2OV0); (o) Paracoccus versutus Am (1ID2);[58] (p) Paracoccus pantotrophus pseudoazurin (pAz) (3ERX);[59] (q) Alcaligenes faecalis pAz (1PAZ);[60] (r) Methylobacterium extorquens pAz (1PMY);[61] (s) Achromobacter cycloclastes pAz (1BQK);[62] (t) Pseudomonas putida azurin (Az) (1NWO);[63] (u) Pseudomonas fluorescens Az (1JOI);[64] (v) Alcaligenes faecalis Az (2IAA);[65] (w) Pseudomonas aeruginosa Az (5AZU);[66] (x) Achromobacter xylosoxidans Az-II (2CCW);[67] (y) Achromobacter xylosoxidans Az-I (1RKR);[68] (z) Methylomonas sp. J Az (1CUO);[69] (aa) Alcaligenes denitrificans Az (1AZC);[70] (bb) Chloroflexus aurantiacus auracyanin-A (2AAN); (cc) Chloroflexus aurantiacus auracyanin-B (1QHQ);[71] (dd) Acidithiobacillus ferrooxidans rusticyanin (1RCY).[72]
Figure 2
Figure 2
Polypeptide ribbon diagrams of copper nitrite reductases (NiR) highlighting locations of the copper centers (spheres) and Tyr/Trp chains with 5-Å (red) ET cutoff distances: (a) Achromobacter cycloclastes (PDB ID 2BW4);[73] (b) Alcaligenes faecalis (1SNR);[74] (c) Alcaligenes xylosoxidans (1OE1);[75] (d) Geobacillus kaustophilus (3WI9);[76] (e) Geobacillus thermodenitrificans (4ZK8);[77] (f) Hyphomicrobium denitrificans (2DV6);[78] (g) Nitrosomonas europaea (4KNU);[79] (h) Neisseria gonorrhoeae (1KBV);[80] (i) Rhodobacter sphaeroides (1ZV2).[81] The upper three Cu centers are the type 1 sites; the Cu atoms in the middle of the structures are the type 2 sites.
Figure 3
Figure 3
Polypeptide ribbon diagram of the small 2dMCO from Streptomycese coelicolor (PDB ID 3KW8).[46b, 82] Copper centers are shown as spheres; Tyr/Trp clusters are shown in red (5-Å ET distance) and green (7.5 Å). The type 1 Cu centers are at the top of the structure; the TNC Cu centers are in the midlevel region. The Tyr108/Trp284 clusters lie below the TNC, toward the periphery of the enzyme.
Figure 4
Figure 4
Polypeptide ribbon diagrams of copper two-domain multicopper oxidases (2dMCO) highlighting locations of the copper centers (spheres) and Tyr/Trp chains with 5-Å (red) ET cutoff distances: (a) Amycolatopsis sp. ATCC 39116 (PDB ID 3T9W);[40a] (b) Streptomyces viridosporus (3TAS);[40a] (c) Streptomyces viridochromogenes (4N8U); (d) Streptomyces sviceus (4M3H);[42] (e) Streptomyces lividans (4GYB); (f) Streptomyces coelicolor (3KW8);[46b, 82] (g) Nitrosomonas europaea (3G5W);[44] (h) Arthrobacter sp. FB24 (3GDC). Type 1 Cu centers appear in the upper portions of the structures; the TNC Cu centers are in the midlevel region.
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