NMR solution structure of the neurotrypsin Kringle domain

Biochemistry. 2008 Nov 25;47(47):12290-8. doi: 10.1021/bi800555z.

Abstract

Neurotrypsin is a multidomain protein that serves as a brain-specific serine protease. Here we report the NMR structure of its kringle domain, NT/K. The data analysis was performed with the BACUS (Bayesian analysis of coupled unassigned spins) algorithm. This study presents the first application of BACUS to the structure determination of a 13C unenriched protein for which no prior experimental 3D structure was available. NT/K adopts the kringle fold, consisting of an antiparallel beta-sheet bridged by an overlapping pair of disulfides. The structure reveals the presence of a surface-exposed left-handed polyproline II helix that is closely packed to the core beta-structure. This feature distinguishes NT/K from other members of the kringle fold and points toward a novel functional role for a kringle domain. Functional divergence among kringle domains is discussed on the basis of their surface and electrostatic characteristics.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bayes Theorem
  • Kringles*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Rats
  • Sequence Alignment
  • Serine Endopeptidases / chemistry*
  • Solutions

Substances

  • Solutions
  • Serine Endopeptidases
  • neurotrypsin

Associated data

  • PDB/1PK4
  • PDB/2FD6
  • PDB/2HPP
  • PDB/2K4R
  • PDB/2K51