Crystal structure of nickel-containing superoxide dismutase reveals another type of active site

Abstract

Superoxide dismutases (SODs, EC 1.15.1.1) are ubiquitous enzymes that efficiently catalyze the dismutation of superoxide radical anions to protect biological molecules from oxidative damage. The crystal structure of nickel-containing SOD (NiSOD) from Streptomyces seoulensis was determined for the resting, x-ray-reduced, and thiosulfate-reduced enzyme state. NiSOD is a homohexamer consisting of four-helix-bundle subunits. The catalytic center resides in the N-terminal active-site loop, where a Ni(III) ion is coordinated by the amino group of His-1, the amide group of Cys-2, two thiolate groups of Cys-2 and Cys-6, and the imidazolate of His-1 as axial ligand that is lost in the chemically reduced state as well as after x-ray-induced reduction. This structure represents a third class of SODs concerning the catalytic metal species, subunit structure, and oligomeric organization. It adds a member to the small number of Ni-metalloenzymes and contributes with its Ni(III) active site to the general understanding of Ni-related biochemistry. NiSOD is shown to occur also in bacteria other than Streptomyces and is predicted to be present in some cyanobacteria.

Molecular cloning, characterization and expression analysis of cytoplasmic Cu/Zn-superoxid dismutase (SOD) from pearl oyster Pinctada fucata

“…Superoxide dismutase (EC 1.15.1.1) is divided into four distinct groups according to their metal content: iron SOD (FeSOD), manganese SOD (MnSOD), copper/zinc SOD (Cu/Zn SOD), and nickel SOD (NiSOD). MnSOD and Cu/Zn SOD are found in both prokaryotes and eukaryotes, FeSOD is found in prokaryotes and plants [1], and NiSOD has recently been purified from several aerobic soil bacteria of Streptomyces [2]. SOD is one of the sensitive biomarker to indicate organisms being under stress [3,4].…”

“…One major strategy to combat disease problem is to identify disease resistance genes and employ them for genetic improvement of cultured stock. Therefore, the aims of the present study were (1) to determine the nucleotide sequence of Cu/Zn SOD from the pearl oyster P. fucata and compare its deduced amino acid sequence to other known Cu/Zn SOD proteins; (2) to examine the expression of pfSOD in various tissues; and (3) to evaluate pfSOD expression after LPS challenge.…”

Nucleophilicity of zinc-bound thiolates

“…[1][2][3] For example, nature utilizes iron-and nickel-ligated thiolates to promote superoxide reductase [4] and superoxide dismutase [5,6] functions, respectively.…”

Identificação dos determinantes estruturais de Fe/MnSODs necessários a especificidade por metal.

“…As estruturas cristalográficas de duas NiSODs, de S. seoulenses e S. coelicolor, foram resolvidas por dois grupos distintos (51,52) que mostraram a organização homohexamérica da enzima além da presença de um motivo de nove aminoácidos (His-Cys-X-X-Pro-Cys-Gly-X-Tyr) na porção catalítica N-terminal. Esses resíduos formam um gancho para complexação de íons níquel e provê interações essenciais para ligação do metal e catálise.…”