The active site cysteine of arginine kinase: structural and functional analysis of partially active mutants

Biochemistry
James L GattisMichael S Chapman

Abstract

Arginine kinase buffers cellular ATP levels by catalyzing reversible phosphoryl transfer between ATP and arginine. A conserved cysteine has long been thought important in catalysis. Here, cysteine 271 of horseshoe crab arginine kinase has been mutated to serine, alanine, asparagine, or aspartate. Catalytic turnover rates were 0.02-1.0% of wild type, but the activity of uncharged mutations could be partially rescued with chloride. Steady-state binding constants were slightly increased, more so for phospho-L-arginine than ADP. Substrate binding synergy observed in many phosphagen kinases was reduced or eliminated in mutant enzymes. The crystallographic structure of the alanine mutant at 2.3 A resolution, determined as a transition state analogue complex with arginine, nitrate, and MgADP, was nearly identical to wild type. Enzyme-substrate interactions are maintained as in wild type, and substrates remain at least roughly aligned for in-line phosphoryl transfer. Homology models with serine, asparagine, or aspartate replacing the active site cysteine similarly show only minor structural changes. Most striking, however, is the presence in the C271A mutant crystallographic structure of a chloride ion within 3.5 A of the nonreactive N...Continue Reading

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Citations

Oct 1, 2013·International Journal of Biological Macromolecules·Oluyomi Stephen Adeyemi, Chris George Whiteley
Jul 26, 2011·Journal of Helminthology·M NagatakiT Agatsuma
Mar 24, 2011·Biochemistry·Omar DavulcuMichael S Chapman
Jan 8, 2011·The Journal of Biological Chemistry·D Jeffrey BushMichael S Chapman
Jan 18, 2006·Journal of Molecular Microbiology and Biotechnology·Janine Kirstein, Kürşad Turgay
Apr 5, 2005·Critical Reviews in Biochemistry and Molecular Biology·Michael J McLeish, George L Kenyon
Sep 22, 2012·Biochemical and Biophysical Research Communications·Shawn A ClarkMichael S Chapman
Sep 15, 2009·Bioorganic & Medicinal Chemistry·Daniel I PerezAna Martínez
Aug 16, 2008·International Journal of Biological Macromolecules·Qing-Yun WuXiao-Yun Wang
Aug 11, 2007·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Qing-Yun WuXiao-Yun Wang
Jun 27, 2007·International Journal of Biological Macromolecules·Hua-Wei HeHai-Meng Zhou
Jun 1, 2006·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·Kouji UdaTomohiko Suzuki
Jul 26, 2005·International Journal of Biological Macromolecules·Zhao FengWang Xicheng
Dec 25, 2012·International Journal of Biological Macromolecules·Wei-Dong WangGuo-Lin Zou
Apr 22, 2011·International Journal of Biological Macromolecules·Na LiuJi-Cheng Pan
Sep 23, 2014·PloS One·Jean C SummertonMichael S Chapman
May 13, 2017·Journal of Structural Biology·Omar DavulcuMichael S Chapman
Mar 3, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Janusz J PetkowskiSara Seager
Apr 10, 2019·Nature Chemical Biology·Marcin J SuskiewiczTim Clausen
Apr 11, 2019·Journal of Agricultural and Food Chemistry·Xue-Jiao MeiGuang-Ming Liu

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