Name
Title | ||
|---|---|---|
β-Amyloid and Neprilysin Computational Studies Identify Critical Residues Implicated in Binding Specificity. |
Abstract | ||
|---|---|---|
The zinc metalloprotease neprilysin (NEP) promiscuously degrades small bioactive peptides. NEP is among a select group of metalloenzymes that degrade the amyloid beta-peptide (A beta) in vivo and in situ. Since accumulation of neurotoxic A beta aggregates in the brain appears to be a causative agent in the pathophysiology of Alzheimer's disease (AD), increased clearance of A beta resulting from overexpression of NEP exhibits therapeutic potential for AD. However, higher NEP peptidase activity may be harmful without an increased specificity for A beta over other competing substrates. Crystal structures of NEP-inhibitor complexes and their characterization have highlighted potential amino acid interactions involved in substrate binding and are used as templates to guide our methodology in docking A beta in NEP. Results from protein-ligand docking calculations predict S2' subsite residues Arg 102 and Arg 110 of NEP participate in specific interactions with A beta. These interactions provide insight into developing NEP specificity for A beta. |
Year | DOI | Venue |
|---|---|---|
2014 | 10.1021/ci500015m | JOURNAL OF CHEMICAL INFORMATION AND MODELING |
DocType | Volume | Issue |
Journal | 54 | 4 |
ISSN | Citations | PageRank |
1549-9596 | 0 | 0.34 |
References | Authors | |
0 | 3 | |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Darrick Pope | 1 | 0 | 0.34 |
| Jeffry D. Madura | 2 | 5 | 2.22 |
| Michael Cascio | 3 | 0 | 0.68 |