The structure of lombricine kinase: Implications for phosphagen kinase conformational changes

D. Jeffrey Bush, Olga Kirillova, Shawn A. Clark, Omar Davulcu, Felcy Fabiola, Qing Xie, Thayumanasamy Somasundaram, W. Ross Ellington, Michael Chapman

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Lombricine kinase is a member of the phosphagen kinase family and a homolog of creatine and arginine kinases, enzymes responsible for buffering cellular ATP levels. Structures of lombricine kinase from the marine worm Urechis caupo were determined by x-ray crystallography. One form was crystallized as a nucleotide complex, and the other was substrate-free. The two structures are similar to each other and more similar to the substrate-free forms of homologs than to the substrate-bound forms of the other phosphagen kinases. Active site specificity loop 309-317, which is disordered in substrate-free structures of homologs and is known from the NMR of arginine kinase to be inherently dynamic, is resolved in both lombricine kinase structures, providing an improved basis for understanding the loop dynamics. Phosphagen kinases undergo a segmented closing on substrate binding, but the lombricine kinase ADP complex is in the open form more typical of substrate-free homologs. Through a comparison with prior complexes of intermediate structure, a correlation was revealed between the overall enzyme conformation and the substrate interactions of His 178. Comparative modeling provides a rationale for the more relaxed specificity of these kinases, of which the natural substrates are among the largest of the phosphagen substrates.

Original languageEnglish (US)
Pages (from-to)9338-9350
Number of pages13
JournalJournal of Biological Chemistry
Volume286
Issue number11
DOIs
StatePublished - Mar 18 2011

Fingerprint

lombricine kinase
Phosphotransferases
Arginine Kinase
Substrates
Crystallography
Enzymes
Creatine Kinase
Adenosine Diphosphate
Catalytic Domain
Nucleotides
Adenosine Triphosphate
X-Rays

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

The structure of lombricine kinase : Implications for phosphagen kinase conformational changes. / Bush, D. Jeffrey; Kirillova, Olga; Clark, Shawn A.; Davulcu, Omar; Fabiola, Felcy; Xie, Qing; Somasundaram, Thayumanasamy; Ellington, W. Ross; Chapman, Michael.

In: Journal of Biological Chemistry, Vol. 286, No. 11, 18.03.2011, p. 9338-9350.

Research output: Contribution to journalArticle

Bush, DJ, Kirillova, O, Clark, SA, Davulcu, O, Fabiola, F, Xie, Q, Somasundaram, T, Ellington, WR & Chapman, M 2011, 'The structure of lombricine kinase: Implications for phosphagen kinase conformational changes', Journal of Biological Chemistry, vol. 286, no. 11, pp. 9338-9350. https://doi.org/10.1074/jbc.M110.202796
Bush, D. Jeffrey ; Kirillova, Olga ; Clark, Shawn A. ; Davulcu, Omar ; Fabiola, Felcy ; Xie, Qing ; Somasundaram, Thayumanasamy ; Ellington, W. Ross ; Chapman, Michael. / The structure of lombricine kinase : Implications for phosphagen kinase conformational changes. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 11. pp. 9338-9350.
@article{a29e02a23f5e4b7e9f3f074ff3de4661,
title = "The structure of lombricine kinase: Implications for phosphagen kinase conformational changes",
abstract = "Lombricine kinase is a member of the phosphagen kinase family and a homolog of creatine and arginine kinases, enzymes responsible for buffering cellular ATP levels. Structures of lombricine kinase from the marine worm Urechis caupo were determined by x-ray crystallography. One form was crystallized as a nucleotide complex, and the other was substrate-free. The two structures are similar to each other and more similar to the substrate-free forms of homologs than to the substrate-bound forms of the other phosphagen kinases. Active site specificity loop 309-317, which is disordered in substrate-free structures of homologs and is known from the NMR of arginine kinase to be inherently dynamic, is resolved in both lombricine kinase structures, providing an improved basis for understanding the loop dynamics. Phosphagen kinases undergo a segmented closing on substrate binding, but the lombricine kinase ADP complex is in the open form more typical of substrate-free homologs. Through a comparison with prior complexes of intermediate structure, a correlation was revealed between the overall enzyme conformation and the substrate interactions of His 178. Comparative modeling provides a rationale for the more relaxed specificity of these kinases, of which the natural substrates are among the largest of the phosphagen substrates.",
author = "Bush, {D. Jeffrey} and Olga Kirillova and Clark, {Shawn A.} and Omar Davulcu and Felcy Fabiola and Qing Xie and Thayumanasamy Somasundaram and Ellington, {W. Ross} and Michael Chapman",
year = "2011",
month = "3",
day = "18",
doi = "10.1074/jbc.M110.202796",
language = "English (US)",
volume = "286",
pages = "9338--9350",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "11",

}

TY - JOUR

T1 - The structure of lombricine kinase

T2 - Implications for phosphagen kinase conformational changes

AU - Bush, D. Jeffrey

AU - Kirillova, Olga

AU - Clark, Shawn A.

AU - Davulcu, Omar

AU - Fabiola, Felcy

AU - Xie, Qing

AU - Somasundaram, Thayumanasamy

AU - Ellington, W. Ross

AU - Chapman, Michael

PY - 2011/3/18

Y1 - 2011/3/18

N2 - Lombricine kinase is a member of the phosphagen kinase family and a homolog of creatine and arginine kinases, enzymes responsible for buffering cellular ATP levels. Structures of lombricine kinase from the marine worm Urechis caupo were determined by x-ray crystallography. One form was crystallized as a nucleotide complex, and the other was substrate-free. The two structures are similar to each other and more similar to the substrate-free forms of homologs than to the substrate-bound forms of the other phosphagen kinases. Active site specificity loop 309-317, which is disordered in substrate-free structures of homologs and is known from the NMR of arginine kinase to be inherently dynamic, is resolved in both lombricine kinase structures, providing an improved basis for understanding the loop dynamics. Phosphagen kinases undergo a segmented closing on substrate binding, but the lombricine kinase ADP complex is in the open form more typical of substrate-free homologs. Through a comparison with prior complexes of intermediate structure, a correlation was revealed between the overall enzyme conformation and the substrate interactions of His 178. Comparative modeling provides a rationale for the more relaxed specificity of these kinases, of which the natural substrates are among the largest of the phosphagen substrates.

AB - Lombricine kinase is a member of the phosphagen kinase family and a homolog of creatine and arginine kinases, enzymes responsible for buffering cellular ATP levels. Structures of lombricine kinase from the marine worm Urechis caupo were determined by x-ray crystallography. One form was crystallized as a nucleotide complex, and the other was substrate-free. The two structures are similar to each other and more similar to the substrate-free forms of homologs than to the substrate-bound forms of the other phosphagen kinases. Active site specificity loop 309-317, which is disordered in substrate-free structures of homologs and is known from the NMR of arginine kinase to be inherently dynamic, is resolved in both lombricine kinase structures, providing an improved basis for understanding the loop dynamics. Phosphagen kinases undergo a segmented closing on substrate binding, but the lombricine kinase ADP complex is in the open form more typical of substrate-free homologs. Through a comparison with prior complexes of intermediate structure, a correlation was revealed between the overall enzyme conformation and the substrate interactions of His 178. Comparative modeling provides a rationale for the more relaxed specificity of these kinases, of which the natural substrates are among the largest of the phosphagen substrates.

UR - http://www.scopus.com/inward/record.url?scp=79953187922&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953187922&partnerID=8YFLogxK

U2 - 10.1074/jbc.M110.202796

DO - 10.1074/jbc.M110.202796

M3 - Article

C2 - 21212263

AN - SCOPUS:79953187922

VL - 286

SP - 9338

EP - 9350

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 11

ER -