Small- and large-scale conformational changes of adenylate kinase: a molecular dynamics study of the subdomain motion and mechanics.

Abstract:

:Adenylate kinase, an enzyme that catalyzes the phosphoryl transfer between ATP and AMP, can interconvert between the open and catalytically potent (closed) forms even without binding ligands. Several aspects of the enzyme elasticity and internal dynamics are analyzed here by atomistic molecular dynamics simulations covering a total time span of 100 ns. This duration is sufficiently long to reveal a partial conversion of the enzyme that proceeds through jumps between structurally different substates. The intra- and intersubstates contributions to the enzyme's structural fluctuations are analyzed and compared both in magnitude and directionality. It is found that, despite the structural heterogeneity of the visited conformers, the generalized directions accounting for conformational fluctuations within and across the substates are mutually consistent and can be described by a limited set of collective modes. The functional-oriented nature of the consensus modes is suggested by their good overlap with the deformation vector bridging the open and closed crystal structures. The consistency of adenylate kinase's internal dynamics over timescales wide enough to capture intra- and intersubstates fluctuations adds elements in favor of the recent proposal that the free (apo) enzyme possesses an innate ability to sustain the open/close conformational changes.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Pontiggia F,Zen A,Micheletti C

doi

10.1529/biophysj.108.135467

subject

Has Abstract

pub_date

2008-12-15 00:00:00

pages

5901-12

issue

12

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(08)82005-X

journal_volume

95

pub_type

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