PDBsum entry 1yq4

Oxidoreductase

PDB id: 1yq4

Contents

Protein chains

614 a.a. *

242 a.a. *

140 a.a. *

102 a.a. *

Ligands

FAD

3NP

FES

SF4

F3S

GOL

JZR

HEM

_UQ

PEE ×2

Waters ×575

* Residue conservation analysis

PDB id:

1yq4

Name:

Oxidoreductase

Title:

Avian respiratory complex ii with 3-nitropropionate and ubiquinone

Structure:

Succinate dehydrogenase flavoprotein subunit. Chain: a. Synonym: fp, flavoprotein subunit of complex ii. Succinate dehydrogenase ip subunit. Chain: b. Succinate dehydrogenase cytochrome b, large subunit. Chain: c. Succinate dehydrogenase cytochrome b, small subunit. Chain: d.

Source:

Gallus gallus. Chicken. Organism_taxid: 9031. Organism_taxid: 9031

Biol. unit:

Tetramer (from PQS)

Resolution:

2.33Å R-factor: 0.202 R-free: 0.252

Authors:

L.Huang,G.Sun,D.Cobessi,A.Wang,J.T.Shen,E.Y.Tung,V.E.Anderson, E.A.Berry

Key ref:

L.S.Huang et al. (2006). 3-nitropropionic acid is a suicide inhibitor of mitochondrial respiration that, upon oxidation by complex II, forms a covalent adduct with a catalytic base arginine in the active site of the enzyme. J Biol Chem, 281, 5965-5972. PubMed id: 16371358 DOI: 10.1074/jbc.M511270200

Date:

01-Feb-05 Release date: 20-Dec-05

Protein chain

Q9YHT1  (SDHA_CHICK) -  Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial from Gallus gallus

Seq: 665 a.a.

Struc: 614 a.a.*

Protein chain

Q9YHT2  (SDHB_CHICK) -  Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial from Gallus gallus

Seq: 290 a.a.

Struc: 242 a.a.

Protein chain

D0VWW3  (D0VWW3_CHICK) -  Succinate dehydrogenase cytochrome b560 subunit, mitochondrial from Gallus gallus

Seq: 140 a.a.

Struc: 140 a.a.*

Protein chain

Q5ZIS0  (DHSD_CHICK) -  Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial from Gallus gallus

Seq: 157 a.a.

Struc: 102 a.a.

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chains A, B: E.C.1.1.5.- - ?????
• Enzyme class 3: Chains A, B, C, D: E.C.1.3.5.1 - succinate dehydrogenase.

Pathway:

• Reaction: a quinone + succinate = fumarate + a quinol

quinone (Bound ligand (Het Group name = JZR) matches with 44.44% similarity) + succinate (Bound ligand (Het Group name = 3NP) matches with 55.56% similarity) = fumarate + quinol

• Cofactor: FAD; Iron-sulfur

FAD (Bound ligand (Het Group name = FAD) corresponds exactly) Iron-sulfur

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1074/jbc.M511270200

J Biol Chem 281:5965-5972 (2006)

PubMed id: 16371358

3-nitropropionic acid is a suicide inhibitor of mitochondrial respiration that, upon oxidation by complex II, forms a covalent adduct with a catalytic base arginine in the active site of the enzyme.

L.S.Huang, G.Sun, D.Cobessi, A.C.Wang, J.T.Shen, E.Y.Tung, V.E.Anderson, E.A.Berry.

ABSTRACT

We report three new structures of mitochondrial respiratory Complex II (succinate ubiquinone oxidoreductase, E.C. 1.3.5.1) at up to 2.1 A resolution, with various inhibitors. The structures define the conformation of the bound inhibitors and suggest the residues involved in substrate binding and catalysis at the dicarboxylate site. In particular they support the role of Arg(297) as a general base catalyst accepting a proton in the dehydrogenation of succinate. The dicarboxylate ligand in oxaloacetate-containing crystals appears to be the same as that reported for Shewanella flavocytochrome c treated with fumarate. The plant and fungal toxin 3-nitropropionic acid, an irreversible inactivator of succinate dehydrogenase, forms a covalent adduct with the side chain of Arg(297). The modification eliminates a trypsin cleavage site in the flavoprotein, and tandem mass spectroscopic analysis of the new fragment shows the mass of Arg(297) to be increased by 83 Da and to have the potential of losing 44 Da, consistent with decarboxylation, during fragmentation.

Selected figure(s)

Figure 1.
FIGURE 1. Overall structure of mitochondrial complex II. The stereo ribbon diagram is colored yellow and brown (flavoprotein), green (iron protein), pink (large anchor polypeptide, chain C), and blue (small anchor peptide, chain D). The CAP domain of the flavoprotein is colored brown. The green space-filling model at the intersection between the CAP domain and the rest of the flavoprotein is the malate-like ligand, and the extended blue ball-and-stick model starting just to the right of that is the FAD cofactor. Note the first helix of anchor peptide (Chain C) packs against a helix of the IP.

Figure 4.
FIGURE 4. The dicarboxylate site in the 3-NP-treated enzyme. The density attributed to the ligand has shrunk and moved away from the flavin toward Arg^297 and His^253. It can be modeled by assuming two atoms from the backbone of 3-NP (C-3 and N) fuse with the guanidino group to form a five-membered ring, with loss of the two nitro oxygens. The carboxylate at the other end fits into the clearly forked density branching off the ring. 2F[o] - F[c] map contoured at 1.7 .

The above figures are reprinted from an Open Access publication published by the ASBMB: J Biol Chem (2006, 281, 5965-5972) copyright 2006.

Figures were selected by the author.

Author's comment

These structures confirmed the role of Arg297 in ligand binding (and presumably catalysis) at the dicarboxylate active site. This had been suspected from mutagenesis and from the structure of homologous Flavocytochrome c of Shewanella, but had never been shown before in Complex II superfamily.
Structure 1YQ4 confirms the covalent binding of the plant and fungal toxin 3-nitropropionate, showing that the catalytic base arginine A297 is covalently modified. This is in contrast to a previous model from the lower-resolution structure of porcine complex II with nitropropionate bound.
-Edward Berry