PDBsum entry 1v97

Oxidoreductase

PDB id: 1v97

Contents

Protein chains

1298 a.a. *

Ligands

FES ×4

MTE-MOS ×2

FAD ×2

FYX ×2

ACY ×2

GOL ×8

Metals

_CA ×2

Waters ×2082

* Residue conservation analysis

PDB id:

1v97

Name:

Oxidoreductase

Title:

Crystal structure of bovine milk xanthine dehydrogenase fyx-051 bound form

Structure:

Xanthine dehydrogenase. Chain: a, b. Synonym: xd. Ec: 1.1.1.204

Source:

Bos taurus. Cattle. Organism_taxid: 9913

Biol. unit:

Dimer (from PQS)

Resolution:

1.94Å R-factor: 0.178 R-free: 0.208

Authors:

K.Okamoto,K.Matsumoto,R.Hille,B.T.Eger,E.F.Pai,T.Nishino

Key ref:

K.Okamoto et al. (2004). The crystal structure of xanthine oxidoreductase during catalysis: implications for reaction mechanism and enzyme inhibition. Proc Natl Acad Sci U S A, 101, 7931-7936. PubMed id: 15148401 DOI: 10.1073/pnas.0400973101

Date:

21-Jan-04 Release date: 22-Jun-04

Protein chains

P80457  (XDH_BOVIN) -  Xanthine dehydrogenase/oxidase from Bos taurus

Seq: 1332 a.a.

Struc: 1298 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: E.C.1.17.1.4 - xanthine dehydrogenase.
• Pathway: Xanthine Dehydrogenase
• Reaction: xanthine + NAD⁺ + H2O = urate + NADH + H⁺

xanthine (Bound ligand (Het Group name = MTE) matches with 45.83% similarity) + NAD(+) + H2O = urate + NADH + H(+)

• Cofactor: FAD; Iron-sulfur; Mo cation

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

• Enzyme class 2: E.C.1.17.3.2 - xanthine oxidase.

Pathway:

• Reaction: xanthine + O2 + H2O = urate + H2O2

xanthine (Bound ligand (Het Group name = MTE) matches with 45.83% similarity) + O2 + H2O = urate + H2O2

• Cofactor: FAD; Iron-sulfur; Mo-molybdopterin

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

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: 10.1073/pnas.0400973101

Proc Natl Acad Sci U S A 101:7931-7936 (2004)

PubMed id: 15148401

The crystal structure of xanthine oxidoreductase during catalysis: implications for reaction mechanism and enzyme inhibition.

K.Okamoto, K.Matsumoto, R.Hille, B.T.Eger, E.F.Pai, T.Nishino.

ABSTRACT

Molybdenum is widely distributed in biology and is usually found as a mononuclear metal center in the active sites of many enzymes catalyzing oxygen atom transfer. The molybdenum hydroxylases are distinct from other biological systems catalyzing hydroxylation reactions in that the oxygen atom incorporated into the product is derived from water rather than molecular oxygen. Here, we present the crystal structure of the key intermediate in the hydroxylation reaction of xanthine oxidoreductase with a slow substrate, in which the carbon-oxygen bond of the product is formed, yet the product remains complexed to the molybdenum. This intermediate displays a stable broad charge-transfer band at approximately 640 nm. The crystal structure of the complex indicates that the catalytically labile Mo-OH oxygen has formed a bond with a carbon atom of the substrate. In addition, the MoS group of the oxidized enzyme has become protonated to afford Mo-SH on reduction of the molybdenum center. In contrast to previous assignments, we find this last ligand at an equatorial position in the square-pyramidal metal coordination sphere, not the apical position. A water molecule usually seen in the active site of the enzyme is absent in the present structure, which probably accounts for the stability of this intermediate toward ligand displacement by hydroxide.

Selected figure(s)

Figure 4.
Fig. 4. Stereo representation of the structure in the active site of XDH with bound FYX-051. FYX-051 (magenta), molybdopterin (cyan), and catalytically important amino acid residues (CPK-atom colored) are illustrated as stick models on a ribbon model background.

Figure 7.
Fig. 7. Proposed mechanism initiated by base-assisted nucleophilic attack of Mo--OH on heterocycles, with subsequent hydride transfer to produce the reaction intermediate (c) whose structure has been analyzed in this report. The subsequent oxidation occurs via d or/and e with varying ratio depending on the substrate used.

Figures were selected by an automated process.