Structure of neurolysin reveals a deep channel that limits substrate access

C. Kent Brown, Kevin Madauss, Wei Lian, Moriah R. Beck, W. David Tolbert, David W. Rodgers

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

Abstract

The zinc metallopeptidase neurolysin is shown by x-ray crystallography to have large structural elements erected over the active site region that allow substrate access only through a deep narrow channel. This architecture accounts for specialization of this neuropeptidase to small bioactive peptide substrates without bulky secondary and tertiary structures. In addition, modeling studies indicate that the length of a substrate N-terminal to the site of hydrolysis is restricted to approximately 10 residues by the limited size of the active site cavity. Some structural elements of neurolysin, including a five-stranded β-sheet and the two active site helices, are conserved with other metallopeptidases. The connecting loop regions of these elements, however, are much extended in neurolysin, and they, together with other open coil elements, line the active site cavity. These potentially flexible elements may account for the ability of the enzyme to cleave a variety of sequences.

Original languageEnglish
Pages (from-to)3127-3132
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number6
DOIs
StatePublished - Mar 13 2001

ASJC Scopus subject areas

  • General

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