PDBsum entry 3a7g

Transferase

PDB id: 3a7g

Contents

Protein chain

290 a.a. *

Waters ×461

* Residue conservation analysis

PDB id:

3a7g

Name:

Transferase

Title:

Human mst3 kinase

Structure:

Serine/threonine kinase 24 (ste20 homolog, yeast). Chain: a, b. Fragment: n-terminal kinase domain (unp residues 1-303). Synonym: mst3 kinase. Engineered: yes

Source:

Homo sapiens. Organism_taxid: 9606. Gene: stk24. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.00Å R-factor: 0.199 R-free: 0.247

Authors:

T.P.Ko,W.Y.Jeng,C.I.Liu,M.D.Lai,A.H.J.Wang

Key ref:

T.P.Ko et al. (2010). Structures of human MST3 kinase in complex with adenine, ADP and Mn2+. Acta Crystallogr D Biol Crystallogr, 66, 145-154. PubMed id: 20124694

Date:

26-Sep-09 Release date: 02-Feb-10

Protein chains

Q9Y6E0  (STK24_HUMAN) -  Serine/threonine-protein kinase 24 from Homo sapiens

Seq: 443 a.a.

Struc: 290 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Acta Crystallogr D Biol Crystallogr 66:145-154 (2010)

PubMed id: 20124694

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

T.P.Ko, W.Y.Jeng, C.I.Liu, M.D.Lai, C.L.Wu, W.J.Chang, H.L.Shr, T.J.Lu, A.H.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 provide useful information for the design of potent inhibitors.