PDBsum entry 2c9v

Oxidoreductase

PDB id: 2c9v

Contents

Protein chain

153 a.a. *

Ligands

SO4 ×5

Metals

_NA ×2

_CU ×2

_ZN ×2

Waters ×597

* Residue conservation analysis

PDB id:

2c9v

Name:

Oxidoreductase

Title:

Atomic resolution structure of cu-zn human superoxide dismutase

Structure:

Superoxide dismutase [cu-zn]. Chain: a, f. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: blood. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932

Biol. unit:

Dimer (from PDB file)

Resolution:

1.07Å R-factor: 0.132 R-free: 0.158

Authors:

R.W.Strange,S.V.Antonyuk,M.A.Hough,P.A.Doucette,J.S.Valentine, S.S.Hasnain

Key ref:

R.W.Strange et al. (2006). Variable Metallation of Human Superoxide Dismutase: Atomic Resolution Crystal Structures of Cu-Zn, Zn-Zn and As-isolated Wild-type Enzymes. J Mol Biol, 356, 1152-1162. PubMed id: 16406071 DOI: 10.1016/j.jmb.2005.11.081

Date:

14-Dec-05 Release date: 20-Dec-05

Protein chains

P00441  (SODC_HUMAN) -  Superoxide dismutase [Cu-Zn] from Homo sapiens

Seq: 154 a.a.

Struc: 153 a.a.

Enzyme reactions

• Enzyme class: E.C.1.15.1.1 - superoxide dismutase.
• Reaction: 2 superoxide + 2 H⁺ = H2O2 + O2

2 × superoxide + 2 × H(+) = H2O2 (Bound ligand (Het Group name = SO4) matches with 40.00% similarity) + O2

• Cofactor: Fe cation or Mn(2+) or (Zn(2+) and Cu cation)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.jmb.2005.11.081

J Mol Biol 356:1152-1162 (2006)

PubMed id: 16406071

Variable Metallation of Human Superoxide Dismutase: Atomic Resolution Crystal Structures of Cu-Zn, Zn-Zn and As-isolated Wild-type Enzymes.

R.W.Strange, S.V.Antonyuk, M.A.Hough, P.A.Doucette, J.S.Valentine, S.S.Hasnain.

ABSTRACT

Human Cu-Zn superoxide dismutase (SOD1) protects cells from the effects of oxidative stress. Mutations in SOD1 are linked to the familial form of amyotrophic lateral sclerosis. Several hypotheses for their toxicity involve the mis-metallation of the enzyme. We present atomic-resolution crystal structures and biophysical data for human SOD1 in three metallation states: Zn-Zn, Cu-Zn and as-isolated. These data represent the first atomic-resolution structures for human SOD1, the first structure of a reduced SOD1, and the first structure of a fully Zn-substituted SOD1 enzyme. Recombinantly expressed as-isolated SOD1 contains a mixture of Zn and Cu at the Cu-binding site. The Zn-Zn structure appears to be at least as stable as the correctly (Cu-Zn) metallated enzyme. These data raise the possibility that in a cellular environment with low availability of free copper, Zn-Zn may be the preferred metallation state of SOD1 prior to its interaction with the copper chaperone.

Selected figure(s)

Figure 4.
Figure 4. The water network at the active site of the re-constituted Cu-Zn enzyme, monomer A. A sulphate ion sits on the surface of the molecule at the substrate entry site. A dual-occupancy water molecule (W1) is 2.6 Å from Cu(II) and 3.7 Å from the position of the Cu(I) atom. W1 is linked to the Thr137 O protein backbone via a H bond and to the Gly141 O atom via H bonding to a second water molecule, W2, which is also linked (2.8 Å) to water molecule W3, the Gly141 residue and to a sulphate ion on the protein surface (2.6 Å). W3 forms a long (2.9 Å) H-bond to the Ny group of Arg143. A full-occupancy water molecule, W5, is in direct contact with the protein main chain, linked to the Lys136 O and His63 N atoms. W5 and W3 are linked by W4, which is 4.4 Å from Cu(II). The Gly141 O and Arg143 Ne atoms are bridged by W6. Finally, W7, 5.3 Å from the (Zn site) Zn atom and a highly conserved water molecule in all three structures (and in bovine SOD), has H bonds with the secondary bridge residue Asp124 Od (2.8 Å) and with Gly85 N (2.9 Å) and Gly72 O (2.8 Å) atoms.

Figure 6.
Figure 6. Thermal probability ellipsoids for the active sites of the (a) Cu-Zn, (b) as-isolated and (c) Zn-Zn structures. The sites show only limited anisotropy. The highly anisotropic ellipsoid for Cu(II) in the Cu-Zn structure is indicative of a range of positions adopted by the metal ion.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 356, 1152-1162) copyright 2006.

Figures were selected by an automated process.