PDBsum entry 4xbu

Transferase/peptide

PDB id: 4xbu

Contents

Protein chains

293 a.a.

13 a.a.

Waters ×150

PDB id:

4xbu

Name:

Transferase/peptide

Title:

In vitro crystal structure of pak4 in complex with inka peptide

Structure:

Serine/threonine-protein kinase pak 4. Chain: a. Fragment: unp residues 286-591. Synonym: p21-activated kinase 4,pak-4. Engineered: yes. Protein fam212a. Chain: b. Fragment: unp residues 167-190. Engineered: yes

Source:

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

Resolution:

2.06Å R-factor: 0.201 R-free: 0.243

Authors:

Y.Baskaran,K.C.Ang,P.V.Anekal,W.L.Chan,J.M.Grimes,E.Manser, R.C.Robinson

Key ref:

Y.Baskaran et al. (2015). An in cellulo-derived structure of PAK4 in complex with its inhibitor Inka1. Nat Commun, 6, 8681. PubMed id: 26607847 DOI: 10.1038/ncomms9681

Date:

17-Dec-14 Release date: 02-Dec-15

Protein chain

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

Seq: 591 a.a.

Struc: 293 a.a.

Protein chain

Q96EL1  (INKA1_HUMAN) -  PAK4-inhibitor INKA1 from Homo sapiens

Seq: 287 a.a.

Struc: 13 a.a.

Enzyme reactions

• Enzyme class: Chain A: 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

DOI no: 10.1038/ncomms9681

Nat Commun 6:8681 (2015)

PubMed id: 26607847

An in cellulo-derived structure of PAK4 in complex with its inhibitor Inka1.

Y.Baskaran, K.C.Ang, P.V.Anekal, W.L.Chan, J.M.Grimes, E.Manser, R.C.Robinson.

ABSTRACT

PAK4 is a metazoan-specific kinase acting downstream of Cdc42. Here we describe the structure of human PAK4 in complex with Inka1, a potent endogenous kinase inhibitor. Using single mammalian cells containing crystals 50 μm in length, we have determined the in cellulo crystal structure at 2.95 Å resolution, which reveals the details of how the PAK4 catalytic domain binds cellular ATP and the Inka1 inhibitor. The crystal lattice consists only of PAK4-PAK4 contacts, which form a hexagonal array with channels of 80 Å in diameter that run the length of the crystal. The crystal accommodates a variety of other proteins when fused to the kinase inhibitor. Inka1-GFP was used to monitor the process crystal formation in living cells. Similar derivatives of Inka1 will allow us to study the effects of PAK4 inhibition in cells and model organisms, to allow better validation of therapeutic agents targeting PAK4.