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Title: Structural characterization of Burkholderia pseudomallei adenylate kinase (Adk): Profound asymmetry in the crystal structure of the 'open' state

Abstract

In all organisms adenylate kinases (Adks) play a vital role in cellular energy metabolism and nucleic acid synthesis. Due to differences in catalytic properties between the Adks found in prokaryotes and in the cytoplasm of eukaryotes, there is interest in targeting this enzyme for new drug therapies against infectious bacterial agents. Here we report the 2.1 {angstrom} resolution crystal structure for the 220-residue Adk from Burkholderia pseudomallei (BpAdk), the etiological agent responsible for the infectious disease melioidosis. The general structure of apo BpAdk is similar to other Adk structures, composed of a CORE subdomain with peripheral ATP-binding (ATP{sub bd}) and LID subdomains. The two molecules in the asymmetric unit have significantly different conformations, with a backbone RMSD of 1.46 {angstrom}. These two BpAdk conformations may represent 'open' Adk sub-states along the preferential pathway to the 'closed' substrate-bound state.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
DOE - OFFICE OF SCIENCE
OSTI Identifier:
1014285
Report Number(s):
BNL-91333-2010-JA
Journal ID: ISSN 0006-291X; BBRCA9; R&D Project: BO-070; KP1605010; TRN: US201111%%238
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 394; Journal Issue: 4; Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; ASYMMETRY; CRYSTAL STRUCTURE; CYTOPLASM; ENZYMES; INFECTIOUS DISEASES; METABOLISM; NUCLEIC ACIDS; PHOSPHOTRANSFERASES; RESOLUTION; SYNTHESIS; Adenylate kinase; Circular dichroism; Conformational transition intermediates; Melioidosis; X-ray crystallography

Citation Formats

Buchko, G W, Robinson, H, Abendroth, J, Staker, B L, and Myler, P J. Structural characterization of Burkholderia pseudomallei adenylate kinase (Adk): Profound asymmetry in the crystal structure of the 'open' state. United States: N. p., 2010. Web. doi:10.1016/j.bbrc.2010.03.112.
Buchko, G W, Robinson, H, Abendroth, J, Staker, B L, & Myler, P J. Structural characterization of Burkholderia pseudomallei adenylate kinase (Adk): Profound asymmetry in the crystal structure of the 'open' state. United States. doi:10.1016/j.bbrc.2010.03.112.
Buchko, G W, Robinson, H, Abendroth, J, Staker, B L, and Myler, P J. Fri . "Structural characterization of Burkholderia pseudomallei adenylate kinase (Adk): Profound asymmetry in the crystal structure of the 'open' state". United States. doi:10.1016/j.bbrc.2010.03.112.
@article{osti_1014285,
title = {Structural characterization of Burkholderia pseudomallei adenylate kinase (Adk): Profound asymmetry in the crystal structure of the 'open' state},
author = {Buchko, G W and Robinson, H and Abendroth, J and Staker, B L and Myler, P J},
abstractNote = {In all organisms adenylate kinases (Adks) play a vital role in cellular energy metabolism and nucleic acid synthesis. Due to differences in catalytic properties between the Adks found in prokaryotes and in the cytoplasm of eukaryotes, there is interest in targeting this enzyme for new drug therapies against infectious bacterial agents. Here we report the 2.1 {angstrom} resolution crystal structure for the 220-residue Adk from Burkholderia pseudomallei (BpAdk), the etiological agent responsible for the infectious disease melioidosis. The general structure of apo BpAdk is similar to other Adk structures, composed of a CORE subdomain with peripheral ATP-binding (ATP{sub bd}) and LID subdomains. The two molecules in the asymmetric unit have significantly different conformations, with a backbone RMSD of 1.46 {angstrom}. These two BpAdk conformations may represent 'open' Adk sub-states along the preferential pathway to the 'closed' substrate-bound state.},
doi = {10.1016/j.bbrc.2010.03.112},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 394,
place = {United States},
year = {2010},
month = {4}
}