An inhibitor of ribosomal peptidyl transferase using transition-state analogy.

Abstract:

:The phosphoramidate of CCdAp and puromycin (CCdApPuro) is a potent inhibitor of ribosomal peptidyl transferase, as assayed by the fragment reaction. Inhibition is competitive at the ribosomal A-site. CCdApPuro protects P-site-associated bases in the peptidyl transferase loop region of 23S rRNA from carbodiimide modification. The Ki's of structural homologues of CCdApPuro suggest that both the CCdA and puromycin moieties participate in binding. Thus, CCdApPuro appears to bridge the A- and P-sites of the ribosome, implying that substrates are juxtaposed with a geometry suitable for direct reaction during peptidyl transfer.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Welch M,Chastang J,Yarus M

doi

10.1021/bi00002a001

subject

Has Abstract

pub_date

1995-01-17 00:00:00

pages

385-90

issue

2

eissn

0006-2960

issn

1520-4995

journal_volume

34

pub_type

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