PDBsum entry 4hzs

Transferase

PDB id: 4hzs

Contents

Protein chains

319 a.a.

PDB id:

4hzs

Name:

Transferase

Title:

Crystal structure of ack1 kinase domain with c-terminal sh3 domain

Structure:

Activated cdc42 kinase 1. Chain: a, b, c, d. Fragment: protein kinase and sh3 domains (unp residues 115-453). Synonym: ack1, ack-1, tyrosine kinase non-receptor protein 2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tnk2, ack1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

3.23Å R-factor: 0.247 R-free: 0.270

Authors:

K.S.Gajiwala

Key ref:

K.S.Gajiwala et al. (2013). Ack1: activation and regulation by allostery. Plos One, 8, e53994. PubMed id: 23342057

Date:

15-Nov-12 Release date: 06-Feb-13

Protein chains

Q07912  (ACK1_HUMAN) -  Activated CDC42 kinase 1 from Homo sapiens

Seq: 1038 a.a.

Struc: 319 a.a.

Enzyme reactions

• Enzyme class 2: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺
• Enzyme class 3: 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⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

Plos One 8:e53994 (2013)

PubMed id: 23342057

Ack1: activation and regulation by allostery.

K.S.Gajiwala, K.Maegley, R.Ferre, Y.A.He, X.Yu.

ABSTRACT

The non-receptor tyrosine kinase Ack1 belongs to a unique multi-domain protein kinase family, Ack. Ack is the only family of SH3 domain containing kinases to have an SH3 domain following the kinase domain; others have their SH3 domains preceding the kinase domain. Previous reports have suggested that Ack1 does not require phosphorylation for activation and the enzyme activity of the isolated kinase domain is low relative to other kinases. It has been shown to dimerize in the cellular environment, which augments its enzyme activity. The molecular mechanism of activation, however, remains unknown. Here we present structural and biochemical data on Ack1 kinase domain, and kinase domain+SH3 domain that suggest that Ack1 in its monomeric state is autoinhibited, like EGFR and CDK. The activation of the kinase domain may require N-lobe mediated symmetric dimerization, which may be facilitated by the N-terminal SAM domain. Results presented here show that SH3 domain, unlike in Src family tyrosine kinases, does not directly control the activation state of the enzyme. Instead we speculate that the SH3 domain may play a regulatory role by facilitating binding of the MIG6 homologous region to the kinase domain. We postulate that features of Ack1 activation and regulation parallel those of receptor tyrosine kinase EGFR with some interesting differences.