The 1.23 Angstrom structure of Pichia pastoris lysyl oxidase reveals a lysine-lysine cross-link

Acta Crystallogr D Biol Crystallogr. 2006 Sep;62(Pt 9):1073-84. doi: 10.1107/S0907444906026333. Epub 2006 Aug 19.

Abstract

The structure of Pichia pastoris lysyl oxidase (PPLO) in a new crystal form has been refined at 1.23 Angstrom resolution. PPLO, a copper amine oxidase (CuAO) with a 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor, differs from most other members of the CuAO enzyme family in having the ability to oxidize the side chain of lysine residues in a polypeptide. In the asymmetric unit of the crystals, the structure analysis has located residues 43-779 of the polypeptide chain, seven carbohydrate residues, the active-site Cu atom, an imidazole molecule bound at the active site, two buried Ca(2+) ions, five surface Mg(2+) ions, five surface Cl(-) ions and 1045 water molecules. The crystallographic residuals are R = 0.112 and R(free) = 0.146. The TPQ cofactor and several other active-site residues are poorly ordered, in contrast to the surrounding well ordered structure. A covalent cross-link is observed between two lysine residues, Lys778 and Lys66. The cross-link is likely to have been formed by the oxidation of Lys778 followed by a spontaneous reaction with Lys66. The link is modelled as dehydrolysinonorleucine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Copper / chemistry
  • Cross-Linking Reagents / pharmacology
  • Crystallography, X-Ray / methods*
  • Dipeptides / chemistry
  • Glycosylation
  • Ions
  • Lysine / chemistry*
  • Models, Chemical
  • Models, Molecular
  • Molecular Conformation
  • Pichia / enzymology*
  • Protein Conformation
  • Protein-Lysine 6-Oxidase / chemistry*

Substances

  • Cross-Linking Reagents
  • Dipeptides
  • Ions
  • dehydrolysylnorleucine
  • Copper
  • Protein-Lysine 6-Oxidase
  • Lysine