PDBsum entry 4ewh

Transferase/transferase inhibitor

PDB id: 4ewh

Contents

Protein chains

274 a.a.

Ligands

T77 ×2

Waters ×23

PDB id:

4ewh

Name:

Transferase/transferase inhibitor

Title:

Co-crystal structure of ack1 with inhibitor

Structure:

Activated cdc42 kinase 1. Chain: b, a. Synonym: ack-1, tyrosine kinase non-receptor protein 2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tnk2, ack1

Resolution:

2.50Å R-factor: 0.259 R-free: 0.313

Authors:

J.Liu,N.Walker,Z.Wang

Key ref:

X.Jiao et al. (2012). Synthesis and optimization of substituted furo[2,3-d]-pyrimidin-4-amines and 7H-pyrrolo[2,3-d]pyrimidin-4-amines as ACK1 inhibitors. Bioorg Med Chem Lett, 22, 6212-6217. PubMed id: 22929232

Date:

27-Apr-12 Release date: 19-Sep-12

Protein chains

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

Seq: 1038 a.a.

Struc: 274 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

Bioorg Med Chem Lett 22:6212-6217 (2012)

PubMed id: 22929232

Synthesis and optimization of substituted furo[2,3-d]-pyrimidin-4-amines and 7H-pyrrolo[2,3-d]pyrimidin-4-amines as ACK1 inhibitors.

X.Jiao, D.J.Kopecky, J.Liu, J.Liu, J.C.Jaen, M.G.Cardozo, R.Sharma, N.Walker, H.Wesche, S.Li, E.Farrelly, S.H.Xiao, Z.Wang, F.Kayser.

ABSTRACT

Two classes of ACK1 inhibitors, 4,5,6-trisubstituted furo[2,3-d]pyrimidin4-amines and 4,5,6-trisubstituted 7H-pyrrolo[2,3-d]pyrimidin-4-amines, were discovered and evaluated as ACK1 inhibitors. Further structural refinement led to the identification of potent and selective dithiolane inhibitor 37.