PDBsum entry 1bx6

Serine/threonine-protein kinase

PDB id: 1bx6

Contents

Protein chain

339 a.a.

Ligands

BA1

Waters ×305

References listed in PDB file

Key reference

• Title: Crystal structure of the potent natural product inhibitor balanol in complex with the catalytic subunit of camp-Dependent protein kinase.
• Authors: N.Narayana, T.C.Diller, K.Koide, M.E.Bunnage, K.C.Nicolaou, L.L.Brunton, N.H.Xuong, L.F.Ten eyck, S.S.Taylor.
• Ref.: Biochemistry, 1999, 38, 2367-2376. [DOI no: 10.1021/bi9820659]
• PubMed id: 10029530

Abstract

Endogenous protein kinase inhibitors are essential for a wide range of physiological functions. These endogenous inhibitors may mimic peptide substrates as in the case of the heat-stable protein kinase inhibitor (PKI), or they may mimic nucleotide triphosphates. Natural product inhibitors, endogenous to the unique organisms producing them, can be potent exogenous inhibitors against foreign protein kinases. Balanol is a natural product inhibitor exhibiting low nanomolar Ki values against serine and threonine specific kinases, while being ineffective against protein tyrosine kinases. To elucidate balanol's specific inhibitory effects and provide a basis for understanding inhibition-regulated biological processes, a 2.1 A resolution crystal structure of balanol in complex with cAMP-dependent protein kinase (cAPK) was determined. The structure reveals conserved binding regions and displays extensive complementary interactions between balanol and conserved cAPK residues. This report describes the structure of a protein kinase crystallized with a natural ATP mimetic in the absence of metal ions and peptide inhibitor.

Secondary reference #1

• Title: A binary complex of the catalytic subunit of camp-Dependent protein kinase and adenosine further defines conformational flexibility.
• Authors: N.Narayana, S.Cox, X.Nguyen-Huu, L.F.Ten eyck, S.S.Taylor.
• Ref.: Structure, 1997, 5, 921-935. [DOI no: 10.1016/S0969-2126(97)00246-3]
• PubMed id: 9261084

Figure 7.
Figure 7. The C-terminal tail. (a) Schematic picture of the three distinct segments of the C-terminal tail (residues 301-350): the large lobe anchor, the C-terminal gate, and the small lobe anchor. Tyr330 (shown in yellow) makes contact with both the nucleotide and the P -3 arginine in PKI(5-24). (b) The three sections of the C-terminal tail are shown in pink, purple and red in the open mC·I structure; the closed ternary rC·I·ATP is shown in white.

The above figure is reproduced from the cited reference with permission from Cell Press

Secondary reference #2

• Title: Crystal structure of a polyhistidine-Tagged recombinant catalytic subunit of camp-Dependent protein kinase complexed with the peptide inhibitor pki(5-24) and adenosine.
• Authors: N.Narayana, S.Cox, S.Shaltiel, S.S.Taylor, N.Xuong.
• Ref.: Biochemistry, 1997, 36, 4438-4448. [DOI no: 10.1021/bi961947+]
• PubMed id: 9109651

Secondary reference #3

• Title: Crystal structure of the catalytic subunit of camp-Dependent protein kinase complexed with mgatp and peptide inhibitor.
• Authors: J.Zheng, D.R.Knighton, L.F.Ten eyck, R.Karlsson, N.Xuong, S.S.Taylor, J.M.Sowadski.
• Ref.: Biochemistry, 1993, 32, 2154-2161. [DOI no: 10.1021/bi00060a005]
• PubMed id: 8443157

Secondary reference #4

• Title: Expression of the catalytic subunit of camp-Dependent protein kinase in escherichia coli: multiple isozymes reflect different phosphorylation states.
• Authors: F.W.Herberg, S.M.Bell, S.S.Taylor.
• Ref.: Protein Eng, 1993, 6, 771-777.
• PubMed id: 8248101

Secondary reference #5

• Title: Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-Dependent protein kinase.
• Authors: D.R.Knighton, J.H.Zheng, L.F.Ten eyck, V.A.Ashford, N.H.Xuong, S.S.Taylor, J.M.Sowadski.
• Ref.: Science, 1991, 253, 407-414. [DOI no: 10.1126/science.1862342]
• PubMed id: 1862342

Secondary reference #6

• Title: Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-Dependent protein kinase.
• Authors: D.R.Knighton, J.H.Zheng, L.F.Ten eyck, N.H.Xuong, S.S.Taylor, J.M.Sowadski.
• Ref.: Science, 1991, 253, 414-420. [DOI no: 10.1126/science.1862343]
• PubMed id: 1862343