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PMID: 11248043 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Structure of neurolysin reveals a deep channel that limits substrate access.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 6 ·2001-03-13 ·Pages 3127-32

Brown CK, Madauss K, Lian W, Beck MR, Tolbert WD, Rodgers DW

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 beta-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.

MeSH Terms
Binding Sites Crystallography, X-Ray Metalloendopeptidases/chemistry Models, Molecular Protein Structure, Tertiary Substrate Specificity
Chemicals
Metalloendopeptidases neurolysin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Brown C K
Department of Molecular and Cellular Biochemistry and Center for Structural Biology, University of Kentucky, Lexington, KY 40536, USA.
Madauss K
Lian W
Beck M R
Tolbert W D
Rodgers D W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.051633198
Published
2001-03-13
Epub
2001-00-06
Pages
3127-32
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC30618
Subset
IM
Databases
PDB
1I1I
External Links
PubMed source DOI: 10.1073/pnas.051633198 PMC Full Text View journal details
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