NMR dynamics of PSE-4 beta-lactamase: an interplay of ps-ns order and mus-ms motions in the active site.

Abstract:

:The backbone dynamics for the 29.5 kDa class A beta-lactamase PSE-4 is presented. This solution NMR study was performed using multiple field (15)N spin relaxation and amide exchange data in the EX2 regime. Analysis was carried out with the relax program and includes the Lipari-Szabo model-free approach. Showing similarity to the homologous enzyme TEM-1, PSE-4 is very rigid on the ps-ns timescale, although slower mus-ms motions are present for several residues; this is especially true near the active site. However, significant dynamics differences exist between the two homologs for several important residues. Moreover, our data support the presence of a motion of the Omega loop first detected using molecular dynamics simulations on TEM-1. Thus, class A beta-lactamases appear to be a class of highly ordered proteins on the ps-ns timescale despite their efficient catalytic activity and high plasticity toward several different beta-lactam antibiotics. Most importantly, catalytically relevant mus-ms motions are present in the active site, suggesting an important role in catalysis.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Morin S,Gagné SM

doi

10.1016/j.bpj.2009.02.068

subject

Has Abstract

pub_date

2009-06-03 00:00:00

pages

4681-91

issue

11

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(09)00699-7

journal_volume

96

pub_type

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