PDBsum entry 4jdi

Transferase/peptide

PDB id: 4jdi

Contents

Protein chain

290 a.a.

Ligands

ARG-ARG-ARG-ARG-SER-TRP

ANP

Metals

_MG ×2

Waters ×139

PDB id:

4jdi

Name:

Transferase/peptide

Title:

Crystal structure of serine/threonine-protein kinase pak 4 in complex with paktide s peptide substrate

Structure:

Serine/threonine-protein kinase pak 4. Chain: a. Synonym: p21-activated kinase 4, pak-4. Engineered: yes. Paktide s. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: kiaa1142, pak4. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes

Resolution:

1.85Å R-factor: 0.194 R-free: 0.233

Authors:

B.H.Ha,T.J.Boggon

Key ref:

C.Chen et al. (2014). Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity. Mol Cell, 53, 140-147. PubMed id: 24374310 DOI: 10.1016/j.molcel.2013.11.013

Date:

25-Feb-13 Release date: 29-Jan-14

Protein chain

O96013  (PAK4_HUMAN) -  Serine/threonine-protein kinase PAK 4 from Homo sapiens

Seq: 591 a.a.

Struc: 290 a.a.

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⁺

L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] (Bound ligand (Het Group name = ANP) matches with 92.86% similarity) + ADP + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] (Bound ligand (Het Group name = ANP) matches with 92.86% similarity) + ADP + H(+)

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

reference

DOI no: 10.1016/j.molcel.2013.11.013

Mol Cell 53:140-147 (2014)

PubMed id: 24374310

Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity.

C.Chen, B.H.Ha, A.F.Thévenin, H.J.Lou, R.Zhang, K.Y.Yip, J.R.Peterson, M.Gerstein, P.M.Kim, P.Filippakopoulos, S.Knapp, T.J.Boggon, B.E.Turk.

ABSTRACT

Eukaryotic protein kinases are generally classified as being either tyrosine or serine-threonine specific. Though not evident from inspection of their primary sequences, many serine-threonine kinases display a significant preference for serine or threonine as the phosphoacceptor residue. Here we show that a residue located in the kinase activation segment, which we term the "DFG+1" residue, acts as a major determinant for serine-threonine phosphorylation site specificity. Mutation of this residue was sufficient to switch the phosphorylation site preference for multiple kinases, including the serine-specific kinase PAK4 and the threonine-specific kinase MST4. Kinetic analysis of peptide substrate phosphorylation and crystal structures of PAK4-peptide complexes suggested that phosphoacceptor residue preference is not mediated by stronger binding of the favored substrate. Rather, favored kinase-phosphoacceptor combinations likely promote a conformation optimal for catalysis. Understanding the rules governing kinase phosphoacceptor preference allows kinases to be classified as serine or threonine specific based on their sequence.