Structures of human MST3 kinase in complex with adenine, ADP and Mn2+

Acta Crystallographica. Section D, Biological Crystallography
Tzu-Ping KoAndrew H-J Wang

Abstract

The MST family is a subclass of mammalian serine/threonine kinases that are related to the yeast sterile-20 protein and are implicated in regulating cell growth and transformation. The MST3 protein contains a 300-residue catalytic domain and a 130-residue regulatory domain, which can be cleaved by caspase and activated by autophosphorylation, promoting apoptosis. Here, five crystal structures of the catalytic domain of MST3 are presented, including a complex with ADP and manganese, a unique cofactor preferred by the enzyme, and a complex with adenine. Similar to other protein kinases, the catalytic domain of MST3 folds into two lobes: the smaller N lobe forms the nucleotide-binding site and the larger C lobe recognizes the polypeptide substrate. The bound ADP and Mn(2+) ions are covered by a glycine-rich loop and held in place by Asn149 and Asp162. A different orientation was observed for the ligand in the MST3-adenine complex. In the activation loop, the side chain of Thr178 is phosphorylated and is sandwiched by Arg143 and Arg176. Comparison of this structure with other similar kinase structures shows a 180 degrees rotation of the loop, leading to activation of the enzyme. The well defined protein-ligand interactions also pro...Continue Reading

References

Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Jan 1, 1981·Advances in Protein Chemistry·J S Richardson
Nov 14, 1997·The Journal of Biological Chemistry·K Schinkmann, J Blenis
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Dec 26, 2001·Chemical Reviews·D A JohnsonS S Taylor
Jul 11, 2002·The Journal of Biological Chemistry·Chi-Ying F HuangChiun-Jye Yuan
Mar 20, 2004·Science·Martin E M NobleLouise N Johnson
Nov 16, 2004·Nature Structural & Molecular Biology·Jeffrey F OhrenCharles A Hasemann
May 17, 2005·Structure·Ming LeiStephen C Harrison
May 23, 2007·Proceedings of the National Academy of Sciences of the United States of America·Eunha HwangChaejoon Cheong
Jul 14, 2007·Trends in Biochemical Sciences·Antony W OliverLaurence H Pearl
Oct 24, 2007·Chemical Reviews·Elizabeth J GoldsmithJohn M Humphreys
Feb 8, 2008·Cellular Signalling·Pin LingMing-Derg Lai
Jun 10, 2008·Current Molecular Medicine·Maria K Lehtinen, Azad Bonni
Jan 15, 2009·Structure·Xiaoshan MinElizabeth J Goldsmith
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Dec 27, 2011·Plant & Cell Physiology·Young-Il ParkHyun Ho Park
Aug 24, 2010·PloS One·Christopher J RecordWen Hwa Lee
Jan 11, 2012·The Biochemical Journal·Stephen J FullerPeter H Sugden
Jan 9, 2013·Biochemical and Biophysical Research Communications·Youcef MehellouJonathan M Elkins
Mar 23, 2011·The EMBO Journal·Beatrice M FilippiDario R Alessi
Aug 1, 2014·Biochemistry·Adam C BastidasSusan S Taylor

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