Probing the active site of human manganese superoxide dismutase: the role of glutamine 143

Biochemistry
Y HsiehD N Silverman

Abstract

Structural and biochemical characterization of the nonliganding residue glutamine 143 near the manganese of human Mn superoxide dismutase (hMnSOD), a homotetramer of 22 kDa, reveals a functional role for this residue. In the wild-type protein, the side-chain amide group of Gln 143 is about 5 A from the metal and is hydrogen-bonded to Tyr 34, which is a second prominent side chain adjacent to the metal. We have prepared the site-specific mutant of hMnSOD with the conservative replacement of Gln 143 --> Asn (Q143N). The crystal structure of Q143N shows that the side-chain amide nitrogen of residue 143 is 1.7 A more distant from the manganese than in the wild-type enzyme. The Tyr 34 side-chain hydroxyl in Q143N is also moved to become 0.6 A more distant from the metal due to an additional water molecule. Differential scanning calorimetry showed that Q143N is slightly more stable than the wild-type enzyme with Tm for the main unfolding transition increased by 2 degrees C to 90.7 degrees C. Pulse radiolysis and stopped-flow spectrophotometry reveal that unlike wild-type hMnSOD, which is strongly inhibited by peroxide, Q143N MnSOD exhibits no product inhibition even at concentrations of O2. - in the millimolar range, and its catalysi...Continue Reading

References

May 25, 1977·Journal of Molecular Biology·F C BernsteinM Tasumi
Nov 11, 1987·Nucleic Acids Research·Y BeckJ R Hartman
Jul 5, 1974·Journal of Molecular Biology·P L Privalov, N N Khechinashvili
Nov 7, 1996·Chemical Reviews·P. J. StephensA. Warshel

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Citations

Jul 20, 2012·Archives of Toxicology·José M MatésJavier Márquez
Mar 7, 2009·Biochemistry·J Jefferson P PerryDavid N Silverman
Mar 7, 2013·Inorganic Chemistry·Timothy A JacksonThomas C Brunold
Nov 15, 2011·Journal of the American Chemical Society·Yuewei ShengJoan Selverstone Valentine
Oct 4, 2013·Journal of the American Chemical Society·Eric M GalePeter Caravan
Sep 24, 1999·The Biochemical Journal·L Requena, S Bornemann
Dec 18, 2007·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·P LiuI T Weber
Apr 10, 2003·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Takaaki KamataniTokio Osaki
Dec 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·David A HildemanPhilippa Marrack
Apr 30, 2014·Fish Physiology and Biochemistry·Kai HuXiaoqiu Zhou
Jul 11, 2006·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Louis Noodleman, Wen-Ge Han
Nov 26, 2009·Biochimica Et Biophysica Acta·Anne-Frances MillerSurekha Vathyam
Nov 17, 2009·Biochimica Et Biophysica Acta·J J P PerryJ A Tainer
Nov 17, 2009·Biochimica Et Biophysica Acta·Isabel A Abreu, Diane E Cabelli
Sep 18, 2008·International Journal of Cancer. Journal International Du Cancer·Aldo ManciniJean Rommelaere
Jun 28, 2006·Journal of Computational Chemistry·Lubomír RulísekUlf Ryde
Sep 12, 2014·Particle and Fibre Toxicology·Xiaoyang ZhaoFashui Hong
Nov 26, 2003·The Journal of Biological Chemistry·Amy S HearnDavid N Silverman
Aug 29, 2006·Genome Génome / Conseil National De Recherches Canada·Amy BeltonAtanu Duttaroy
Oct 16, 2002·The Journal of Biological Chemistry·William B Greenleaf, David N Silverman
May 11, 2017·Essays in Biochemistry·Wen Zhu, Nigel G J Richards
Sep 17, 1999·The Journal of Biological Chemistry·C A RamiloD N Silverman
Apr 8, 2021·Nature Communications·Jahaun AzadmaneshGloria E O Borgstahl
Apr 2, 2014·Chemical Reviews·Yuewei ShengJoan Selverstone Valentine
Dec 27, 2005·The Journal of Physical Chemistry. B·Isabel A AbreuDiane E Cabelli
Jul 14, 2007·Journal of the American Chemical Society·Emine YikilmazAnne-Frances Miller
Jun 2, 2004·Biochemistry·William B GreenleafDavid N Silverman
Jul 7, 2005·Inorganic Chemistry·Marciela ScarpelliniVincent L Pecoraro
Oct 5, 2021·Acta Crystallographica. Section D, Structural Biology·Gabriela C Schröder, Flora Meilleur

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