title: Structural comparison of human mammalian ste20-like kinases.
abstract: BACKGROUND
  The serine/threonine mammalian Ste-20 like kinases (MSTs) are key regulators of apoptosis, cellular proliferation as well as polarization. Deregulation of MSTs has been associated with disease progression in prostate and colorectal cancer. The four human MSTs are regulated differently by C-terminal regions flanking the catalytic domains.
  
  
  RESULTS
  We have determined the crystal structure of kinase domain of MST4 in complex with an ATP-mimetic inhibitor. This is the first structure of an inactive conformation of a member of the MST kinase family. Comparison with active structures of MST3 and MST1 revealed a dimeric association of MST4 suggesting an activation loop exchanged mechanism of MST4 auto-activation. Together with a homology model of MST2 we provide a comparative analysis of the kinase domains for all four members of the human MST family.
  
  
  CONCLUSIONS
  The comparative analysis identified new structural features in the MST ATP binding pocket and has also defined the mechanism for autophosphorylation. Both structural features may be further explored for inhibitors design.
  
  
  BACKGROUND
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authors: Structural Genomics Consortium, University of Oxford, Oxford, United Kingdom.
authors: Christopher J
authors: CJ
authors: Record
authors: Apirat
authors: A
authors: Chaikuad
authors: Peter
authors: P
authors: Rellos
authors: Sanjan
authors: S
authors: Das
authors: Ashley C W
authors: AC
authors: Pike
authors: Oleg
authors: O
authors: Fedorov
authors: Brian D
authors: BD
authors: Marsden
authors: Stefan
authors: S
authors: Knapp
authors: Wen Hwa
authors: WH
authors: Lee
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D055503:Protein Multimerization; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D011799:Quinazolines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases