PDBsum entry 1z57

Transferase

PDB id: 1z57

Contents

Protein chain

333 a.a. *

Ligands

DBQ

Waters ×401

* Residue conservation analysis

PDB id:

1z57

Name:

Transferase

Title:

Crystal structure of human clk1 in complex with 10z-hymenialdisine

Structure:

Dual specificity protein kinase clk1. Chain: a. Fragment: residues 148-484. Synonym: cdc like kinase 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: clk1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.70Å R-factor: 0.140 R-free: 0.186

Authors:

J.Debreczeni,S.Das,S.Knapp,A.Bullock,K.Guo,A.Amos,O.Fedorov, A.Edwards,M.Sundstrom,F.Von Delft,F.H.Niesen,L.Ball,F.Sobott, C.Arrowsmith,Structural Genomics Consortium (Sgc)

Key ref:

A.N.Bullock et al. (2009). Kinase domain insertions define distinct roles of CLK kinases in SR protein phosphorylation. Structure, 17, 352-362. PubMed id: 19278650

Date:

17-Mar-05 Release date: 12-Apr-05

Protein chain

P49759  (CLK1_HUMAN) -  Dual specificity protein kinase CLK1 from Homo sapiens

Seq: 484 a.a.

Struc: 333 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.12.1 - dual-specificity 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⁺
  3. L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

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

reference

Structure 17:352-362 (2009)

PubMed id: 19278650

Kinase domain insertions define distinct roles of CLK kinases in SR protein phosphorylation.

A.N.Bullock, S.Das, J.E.Debreczeni, P.Rellos, O.Fedorov, F.H.Niesen, K.Guo, E.Papagrigoriou, A.L.Amos, S.Cho, B.E.Turk, G.Ghosh, S.Knapp.

ABSTRACT

Splicing requires reversible phosphorylation of serine/arginine-rich (SR) proteins, which direct splice site selection in eukaryotic mRNA. These phosphorylation events are dependent on SR protein (SRPK) and cdc2-like kinase (CLK) families. SRPK1 phosphorylation of splicing factors is restricted by a specific docking interaction whereas CLK activity is less constrained. To understand functional differences between splicing factor targeting kinases, we determined crystal structures of CLK1 and CLK3. Intriguingly, in CLKs the SRPK1 docking site is blocked by insertion of a previously unseen helix alphaH. In addition, substrate docking grooves present in related mitogen activating protein kinases (MAPKs) are inaccessible due to a CLK specific beta7/8-hairpin insert. Thus, the unconstrained substrate interaction together with the determined active-site mediated substrate specificity allows CLKs to complete the functionally important hyperphosphorylation of splicing factors like ASF/SF2. In addition, despite high sequence conservation, we identified inhibitors with surprising isoform specificity for CLK1 over CLK3.