Escherichia coli adenylate kinase dynamics: Comparison of elastic network model modes with mode-coupling 15N-NMR relaxation data

N. Alpay Temiz, Eva Meirovitch, Ivet Bahar

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

The dynamics of adenylate kinase of Escherichia coli (AKeco) and its complex with the inhibitor AP5A, are characterized by correlating the theoretical results obtained with the Gaussian Network Model (GNM) and the anisotropic network model (ANM) with the order parameters and correlation times obtained with Slowly Relaxing Local Structure (SRLS) analysis of 15N-NMR relaxation data. The AMPbd and LID domains of AKeco execute in solution large amplitude motions associated with the catalytic reaction Mg+2*ATP + AMP → Mg+2*ADP + ADP. Two sets of correlation times and order parameters were determined by NMR/SRLS for AKeco, attributed to slow (nanoseconds) motions with correlation time τ and low order parameters, and fast (picoseconds) motions with correlation time τ and high order parameters. The structural connotation of these patterns is examined herein by subjecting AKeco and AKeco*AP5A to GNM analysis, which yields the dynamic spectrum in terms of slow and fast modes. The low/high NMR order parameters correlate with the slow/fast modes of the backbone elucidated with GNM. Likewise, τ and τ are associated with fast and slow GNM modes, respectively. Catalysis-related domain motion of AMPbd and LID in AKeco, occurring per NMR with correlation time τ , is associated with the first and second collective slow (global) GNM modes. The ANM-predicted deformations of the unliganded enzyme conform to the functional reconfiguration induced by ligand-binding, indicating the structural disposition (or potential) of the enzyme to bind its substrates. It is shown that NMR/SRLS and GNM/ ANM analyses can be advantageously synthesized to provide insights into the molecular mechanisms that control biological function.

Original languageEnglish (US)
Pages (from-to)468-480
Number of pages13
JournalProteins: Structure, Function and Genetics
Volume57
Issue number3
DOIs
StatePublished - Nov 15 2004

Fingerprint

Adenylate Kinase
Escherichia coli
Nuclear magnetic resonance
Adenosine Diphosphate
Enzymes
Adenosine Monophosphate
Catalysis
Adenosine Triphosphate
Ligands

Keywords

  • Collective modes
  • Conformational changes
  • Gaussian network model
  • Slowly Relaxing Local Structure

Cite this

Escherichia coli adenylate kinase dynamics : Comparison of elastic network model modes with mode-coupling 15N-NMR relaxation data. / Temiz, N. Alpay; Meirovitch, Eva; Bahar, Ivet.

In: Proteins: Structure, Function and Genetics, Vol. 57, No. 3, 15.11.2004, p. 468-480.

Research output: Contribution to journalArticle

@article{0f39e3ca82c1418a8d99b7006e0039fb,
title = "Escherichia coli adenylate kinase dynamics: Comparison of elastic network model modes with mode-coupling 15N-NMR relaxation data",
abstract = "The dynamics of adenylate kinase of Escherichia coli (AKeco) and its complex with the inhibitor AP5A, are characterized by correlating the theoretical results obtained with the Gaussian Network Model (GNM) and the anisotropic network model (ANM) with the order parameters and correlation times obtained with Slowly Relaxing Local Structure (SRLS) analysis of 15N-NMR relaxation data. The AMPbd and LID domains of AKeco execute in solution large amplitude motions associated with the catalytic reaction Mg+2*ATP + AMP → Mg+2*ADP + ADP. Two sets of correlation times and order parameters were determined by NMR/SRLS for AKeco, attributed to slow (nanoseconds) motions with correlation time τ⊥ and low order parameters, and fast (picoseconds) motions with correlation time τ∥ and high order parameters. The structural connotation of these patterns is examined herein by subjecting AKeco and AKeco*AP5A to GNM analysis, which yields the dynamic spectrum in terms of slow and fast modes. The low/high NMR order parameters correlate with the slow/fast modes of the backbone elucidated with GNM. Likewise, τ∥ and τ⊥ are associated with fast and slow GNM modes, respectively. Catalysis-related domain motion of AMPbd and LID in AKeco, occurring per NMR with correlation time τ ⊥, is associated with the first and second collective slow (global) GNM modes. The ANM-predicted deformations of the unliganded enzyme conform to the functional reconfiguration induced by ligand-binding, indicating the structural disposition (or potential) of the enzyme to bind its substrates. It is shown that NMR/SRLS and GNM/ ANM analyses can be advantageously synthesized to provide insights into the molecular mechanisms that control biological function.",
keywords = "Collective modes, Conformational changes, Gaussian network model, Slowly Relaxing Local Structure",
author = "Temiz, {N. Alpay} and Eva Meirovitch and Ivet Bahar",
year = "2004",
month = "11",
day = "15",
doi = "10.1002/prot.20226",
language = "English (US)",
volume = "57",
pages = "468--480",
journal = "Proteins: Structure, Function and Bioinformatics",
issn = "0887-3585",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Escherichia coli adenylate kinase dynamics

T2 - Comparison of elastic network model modes with mode-coupling 15N-NMR relaxation data

AU - Temiz, N. Alpay

AU - Meirovitch, Eva

AU - Bahar, Ivet

PY - 2004/11/15

Y1 - 2004/11/15

N2 - The dynamics of adenylate kinase of Escherichia coli (AKeco) and its complex with the inhibitor AP5A, are characterized by correlating the theoretical results obtained with the Gaussian Network Model (GNM) and the anisotropic network model (ANM) with the order parameters and correlation times obtained with Slowly Relaxing Local Structure (SRLS) analysis of 15N-NMR relaxation data. The AMPbd and LID domains of AKeco execute in solution large amplitude motions associated with the catalytic reaction Mg+2*ATP + AMP → Mg+2*ADP + ADP. Two sets of correlation times and order parameters were determined by NMR/SRLS for AKeco, attributed to slow (nanoseconds) motions with correlation time τ⊥ and low order parameters, and fast (picoseconds) motions with correlation time τ∥ and high order parameters. The structural connotation of these patterns is examined herein by subjecting AKeco and AKeco*AP5A to GNM analysis, which yields the dynamic spectrum in terms of slow and fast modes. The low/high NMR order parameters correlate with the slow/fast modes of the backbone elucidated with GNM. Likewise, τ∥ and τ⊥ are associated with fast and slow GNM modes, respectively. Catalysis-related domain motion of AMPbd and LID in AKeco, occurring per NMR with correlation time τ ⊥, is associated with the first and second collective slow (global) GNM modes. The ANM-predicted deformations of the unliganded enzyme conform to the functional reconfiguration induced by ligand-binding, indicating the structural disposition (or potential) of the enzyme to bind its substrates. It is shown that NMR/SRLS and GNM/ ANM analyses can be advantageously synthesized to provide insights into the molecular mechanisms that control biological function.

AB - The dynamics of adenylate kinase of Escherichia coli (AKeco) and its complex with the inhibitor AP5A, are characterized by correlating the theoretical results obtained with the Gaussian Network Model (GNM) and the anisotropic network model (ANM) with the order parameters and correlation times obtained with Slowly Relaxing Local Structure (SRLS) analysis of 15N-NMR relaxation data. The AMPbd and LID domains of AKeco execute in solution large amplitude motions associated with the catalytic reaction Mg+2*ATP + AMP → Mg+2*ADP + ADP. Two sets of correlation times and order parameters were determined by NMR/SRLS for AKeco, attributed to slow (nanoseconds) motions with correlation time τ⊥ and low order parameters, and fast (picoseconds) motions with correlation time τ∥ and high order parameters. The structural connotation of these patterns is examined herein by subjecting AKeco and AKeco*AP5A to GNM analysis, which yields the dynamic spectrum in terms of slow and fast modes. The low/high NMR order parameters correlate with the slow/fast modes of the backbone elucidated with GNM. Likewise, τ∥ and τ⊥ are associated with fast and slow GNM modes, respectively. Catalysis-related domain motion of AMPbd and LID in AKeco, occurring per NMR with correlation time τ ⊥, is associated with the first and second collective slow (global) GNM modes. The ANM-predicted deformations of the unliganded enzyme conform to the functional reconfiguration induced by ligand-binding, indicating the structural disposition (or potential) of the enzyme to bind its substrates. It is shown that NMR/SRLS and GNM/ ANM analyses can be advantageously synthesized to provide insights into the molecular mechanisms that control biological function.

KW - Collective modes

KW - Conformational changes

KW - Gaussian network model

KW - Slowly Relaxing Local Structure

UR - http://www.scopus.com/inward/record.url?scp=6344231648&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=6344231648&partnerID=8YFLogxK

U2 - 10.1002/prot.20226

DO - 10.1002/prot.20226

M3 - Article

C2 - 15382240

AN - SCOPUS:6344231648

VL - 57

SP - 468

EP - 480

JO - Proteins: Structure, Function and Bioinformatics

JF - Proteins: Structure, Function and Bioinformatics

SN - 0887-3585

IS - 3

ER -