Crystal structure of bovine heart phosphotyrosyl phosphatase at 2.2-A resolution

Biochemistry
M ZhangCynthia V Stauffacher

Abstract

The first X-ray crystallographic structure of a member of the class of low molecular weight (M(r) 18,000) phosphotyrosyl phosphatases is presented. Bovine heart phosphotyrosyl phosphatase (BHPTP) exemplifies this class and is highly homologous (94% sequence identity) to an isoenzyme known as red cell acid phosphatase that is present throughout human tissues. The high-resolution (2.2-A) crystal structure of BHPTP shows that the enzyme consists of a four-strand central parallel beta sheet with alpha helices packed on both sides in a manner characteristic of a Rossmann fold. A bound phosphate ion defines the active site location in a loop of the first beta alpha beta motif at the C-terminus of the beta sheet. The location and enzymatic significance of the residues in the characteristic low molecular weight PTPase active site motif, including the essential arginine (Arg 18) and nucleophilic cysteine (Cys 12), are described. The functional role of a histidine (His 72) suggested previously to be near the active site is defined in the structure, as well as a potential proton donor for the leaving group in the tyrosyl phosphate cleavage. Surface maps of BHPTP define a hydrophobic crevice suitable for phosphotyrosyl peptide binding. Com...Continue Reading

Citations

Sep 1, 1995·Protein Science : a Publication of the Protein Society·H L SchubertM A Saper
Dec 1, 1995·Current Opinion in Structural Biology·D Barford
Nov 14, 1997·Biochimica Et Biophysica Acta·G Ramponi, M Stefani
Nov 1, 1996·Trends in Biochemical Sciences·E B Fauman, M A Saper
Mar 28, 2003·Bioorganic & Medicinal Chemistry·Ping HuangCho Tang
Nov 18, 1998·Current Opinion in Chemical Biology·J M Denu, J E Dixon
Mar 12, 2009·Journal of the American Chemical Society·Jascha BlobelMiquel Pons
Dec 1, 1995·Nature Structural Biology·D BarfordN K Tonks
Jun 20, 1995·Proceedings of the National Academy of Sciences of the United States of America·J M Denu, J E Dixon
May 14, 2005·Antioxidants & Redox Signaling·Annette Salmeen, David Barford
Nov 8, 2001·Proceedings of the National Academy of Sciences of the United States of America·M S BennettX D Su
Aug 8, 2007·Journal of Molecular Biology·Pier Federico GherardiniMichael J E Sternberg
Mar 21, 2007·European Journal of Medicinal Chemistry·David VidalMiquel Pons
Oct 1, 2005·Protein Science : a Publication of the Protein Society·Christin L T GustafsonRobert L Van Etten
Feb 27, 2008·The FEBS Journal·Lydia TaberneroStefan E Szedlacsek
Sep 30, 2006·Protein Science : a Publication of the Protein Society·Dmitri TolkatchevFeng Ni
Dec 25, 2012·BMB Reports·Seung Jun Kim, Seong Eon Ryu
Mar 19, 2013·Biochimica Et Biophysica Acta·Debojit GuhaH S Savithri
Sep 30, 2014·Seminars in Cell & Developmental Biology·Jesse Bakke, Fawaz G Haj
Nov 1, 1996·Cell·J M DenuJ E Dixon
Nov 1, 1995·Chemistry & Biology·W P Taylor, T S Widlanski
Dec 6, 2016·Acta Crystallographica. Section F, Structural Biology Communications·Marco Salomone-StagniStefano Benini
Apr 17, 1998·Critical Reviews in Biochemistry and Molecular Biology·Z Y Zhang
Feb 24, 1995·The Journal of Biological Chemistry·C PokalskyR L Van Etten
Aug 16, 2005·The Journal of Biological Chemistry·Karen E ChristensenRobert E Mackenzie
Jan 24, 2002·The Journal of Biological Chemistry·Daniel F McCainZhong-Yin Zhang

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