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

doi:10.1073/pnas.0308514101

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

^*International School for Advanced Studies, Via Beirut 2-4, I-34014 Trieste, Italy; and ^†Structural Biology Laboratory, Sincrotrone Trieste in Area Science Park, SS. 14 Km 163.5, I-34012 Basovizza, Trieste, Italy; and ^§Laboratory of Biophysics, School of Biological Sciences, and ^¶Institute of Microbiology, Seoul National University, Seoul 151-742, South Korea

Edited by Irwin Fridovich, Duke University Medical Center, Durham, NC, and approved April 27, 2004 (received for review December 19, 2003)

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.

Footnotes

↵ ∥ To whom correspondence may be addressed. E-mail: kangsaou{at}snu.ac.kr or djinovic{at}elettra.trieste.it.
↵ ‡ J.W. and J.-W.L. contributed equally to this work.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviation: SOD, superoxide dismutase.
Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID codes 1Q0D, 1Q0F, 1Q0G, 1Q0K, and 1Q0M).