Analysis of conserved residues of the human puromycin-sensitive aminopeptidase.

Abstract:

:The puromycin-sensitive aminopeptidase (ApPS) is a zinc metallopeptidase involved in the degradation of neuropeptides. Putative catalytic residues of the enzyme, Cys146, Glu338, and Lys396 were mutated, and the resultant mutant enzymes characterized. ApPS C146S exhibited normal catalytic activity, ApPS E338A exhibited decreased substrate binding, and ApPS K396I exhibited decreases in both substrate binding and catalysis. ApPS K396I and ApPS Y394F were analyzed with respect to transition state inhibitor binding. No effect was seen with the K396I mutation, but ApPS Y394F exhibited a 3.3-fold lower affinity for RB-3014, a transition state inhibitor, indicating that Tyr394 is involved in transition state stabilization.

journal_name

Peptides

journal_title

Peptides

authors

Thompson MW,Hersh LB

doi

10.1016/j.peptides.2003.07.012

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

1359-65

issue

9

eissn

0196-9781

issn

1873-5169

pii

S0196978103002778

journal_volume

24

pub_type

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