ScienceDaily (Mar. 9, 2010) — Researchers at the Louisiana State University Health Sciences Center have figured out how ATP is broken down in cells, providing for the first time a clear picture of the key reaction that allows cells in all living things to function and flourish.
.jpg)
Artist's rendering of basic cell structure. (Credit: iStockphoto/Sebastian Kaulitzki)
"ATP is the fuel of life. It's an energy currency molecule -- the most important source of chemical and mechanical energy in living systems," explains Sunyoung Kim, the associate professor who oversaw the research published Feb. 19 in theJournal of Biological Chemistry.
Scientists for decades have worked to understand the critically important reaction but, until now, did not know how proteins in a cell extract and use the energy from ATP.
In its original form, an ATP molecule has three phosphate groups. While it has been known for some time that, for ATP breakdown to occur, the third phosphate group must be attacked by a hydroxide, or a water molecule that has lost one of its protons, it was unknown what actually stripped away that proton, allowing the release of ATP's stores.
The team chose to investigate one particular family of protein machines that break down ATP -- the kinesins.
Kinesins are tiny biological machines that work a lot like car engines, Kim says, travelling up and down cellular roadways in support of several functions, such as cellular division and cargo transport.
...
Read more here/Leia mais aqui: Science Daily
+++++
Courtney L. Parke, Edward J. Wojcik, Sunyoung Kim1 and David K. Worthylake
-Author Affiliations
From the Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112
1 To whom correspondence should be addressed: 1901 Perdido St., New Orleans, LA 70112. Tel.: 504-568-2019; Fax: 504-568-3370; E-mail: skim3@lsuhsc.edu.
Abstract
Motor proteins couple steps in ATP binding and hydrolysis to conformational switching both in and remote from the active site. In our kinesin·AMPPPNP crystal structure, closure of the active site results in structural transformations appropriate for microtubule binding and organizes an orthosteric two-water cluster. We conclude that a proton is shared between the lytic water, positioned for γ-phosphate attack, and a second water that serves as a general base. To our knowledge, this is the first experimental detection of the catalytic base for any ATPase. Deprotonation of the second water by switch residues likely triggers subsequent large scale structural rearrangements. Therefore, the catalytic base is responsible for initiating nucleophilic attack of ATP and for relaying the positive charge over long distances to initiate mechanotransduction. Coordination of switch movements via sequential proton transfer along paired water clusters may be universal for nucleotide triphosphatases with conserved active sites, such as myosins and G-proteins.
Enzymes/ATPases Enzymes/Catalysis Enzymes/Mechanisms Enzymes/Structure
Methods/X-ray Crystallography Molecular Motors Molecular Motors/Kinesin Protein/Conformation
Footnotes
↵* This work was supported, in whole or in part, by National Institutes of Health Grant GM066328 (to E. W.). This work was also supported by funding from Louisiana Board of Regents grants (to D. W. and to S. K.).
↵♦ This article was selected as a Paper of the Week.
The atomic coordinates and structure factors (code 3HQD) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
↵ The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1, Tables S1 and S2, and Movies S1 and S2.
↵3 B. Jun and S. Kim, manuscript in preparation.
↵2 The abbreviations used are:AMPPNP5′-adenylylimidodiphosphateNTPasenucleotide triphosphataseMTmicrotubuleMES4-morpholineethanesulfonic acidPIPES1,4-piperazinediethanesulfonic acidcryo-EMcryo-electron microscopy.
Received September 29, 2009.
Revision received November 16, 2009.
© 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
Footnotes
↵* This work was supported, in whole or in part, by National Institutes of Health Grant GM066328 (to E. W.). This work was also supported by funding from Louisiana Board of Regents grants (to D. W. and to S. K.).
↵♦ This article was selected as a Paper of the Week.
The atomic coordinates and structure factors (code 3HQD) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
↵ The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1, Tables S1 and S2, and Movies S1 and S2.
↵3 B. Jun and S. Kim, manuscript in preparation.
↵2 The abbreviations used are:AMPPNP5′-adenylylimidodiphosphateNTPasenucleotide triphosphataseMTmicrotubuleMES4-morpholineethanesulfonic acidPIPES1,4-piperazinediethanesulfonic acidcryo-EMcryo-electron microscopy.
Received September 29, 2009.
Revision received November 16, 2009.
© 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
+++++
Professores, pesquisadores e alunos de universidades públicas e privadas com acesso ao site CAPES/Periódicos podem ler gratuitamente este artigo do The Journal of Biological Chemistry e de mais 22.440 publicações científicas.
