PDBsum entry 1ctp

Transferase/transferase inhibitor

PDB id: 1ctp

Contents

Protein chains

333 a.a. *

18 a.a. *

Ligands

MYR

Waters ×2

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: Structure of the mammalian catalytic subunit of camp-Dependent protein kinase and an inhibitor peptide displays an open conformation.
• Authors: R.Karlsson, J.Zheng, N.Xuong, S.S.Taylor, J.M.Sowadski.
• Ref.: Acta Crystallogr D Biol Crystallogr, 1993, 49, 381-388. [DOI no: 10.1107/S0907444993002306]
• PubMed id: 15299513

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a percentage match of 96%.

Abstract

The crystal structure of a binary complex of the porcine heart catalytic (C) subunit of cAMP-dependent protein kinase (space group P4(1)32; a = 171.5 A) complexed with a di-iodinated peptide inhibitor, PKI(5-24), has been solved and refined to 2.9 A resolution with an overall R of 21.1%. The r.m.s. deviations from ideal bond lengths and angles are 0.022 A and 4.3 degrees. A single isotropic B of 17 A(2) was used for all atoms. The structure solution was carried out initially by molecular replacement of electron density followed by refinement against atomic coordinates from orthorhombic crystals of a binary complex of the mouse recombinant enzyme previously described [Knighton, Zheng, Ten Eyck, Ashford, Xuong, Taylor & Sowadski (1991). Science, 253, 407-414]. The most striking difference between the two crystal structures is a large displacement of the small lobe of the enzyme. In the cubic crystal, the beta-sheet of the small lobe is rotated by 15 degrees and translated by 1.9 A with respect to the orthorhombic crystal. Possible explanations for why this binary complex crystallized in an open conformation in contrast to a similar binary complex of the recombinant enzyme are discussed. This study demonstrates that considerable information about parts of a crystal structure can be obtained without a complete crystal structure analysis. Specifically, the six rigid-group parameters of a poly alanine model of the beta-structure were obtained satisfactorily from a crystal structure by refinement of difference Fourier coefficients based on an approximate partial structure model.

Figure 2.
ig. 2. Stereoview of the environ- ment of His87. The small lobe is indicated in red and the large lobe in blue. The inhibitor is indicated in black. (a) In the recombinant mouse C subunit, His87 of the small lobe interacts with the stble phosphoryation site of Thr197 of the large lobe and the carbonyl group of the main chain of Glu86 interacts with the side chain of Asng0. (b) In the pocine heart C subunit, His87 moves away from the phosphate of Thr197 and the side chain of Asng0 of the small lobe interacts with the carbonyl of Ala188 of the large lobe. istances are given in A.

The above figure is reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1993, 49, 381-388) copyright 1993.

Secondary reference #1

• 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 #2

• Title: 2.0 a refined crystal structure of the catalytic subunit of camp-Dependent protein kinase complexed with a peptide inhibitor and detergent.
• Authors: D.R.Knighton, S.M.Bell, J.Zheng, L.F.Ten eyck, N.H.Xuong, S.S.Taylor, J.M.Sowadski.
• Ref.: Acta Crystallogr D Biol Crystallogr, 1993, 49, 357-361. [DOI no: 10.1107/S0907444993000502]
• PubMed id: 15299526

Figure 1.
Fig. 1. C:PKI(5-24) C a backbone trace. The PKI(5-24) peptide inhibitor is shown in red. The MEGA-8 detergent, modeled as n-octane, is shown in blue in the lower left. In green is the superimposed C a trace of the superseded 2.7 ,/k 1CPK model for residues 54-67 and 307-341.

The above figure is reproduced from the cited reference with permission from the IUCr

Secondary reference #3

• Title: 2.2 a refined crystal structure of the catalytic subunit of camp-Dependent protein kinase complexed with mnatp and a peptide inhibitor.
• Authors: J.Zheng, E.A.Trafny, D.R.Knighton, N.H.Xuong, S.S.Taylor, L.F.Ten eyck, J.M.Sowadski.
• Ref.: Acta Crystallogr D Biol Crystallogr, 1993, 49, 362-365. [DOI no: 10.1107/S0907444993000423]
• PubMed id: 15299527

Figure 2.
Fig. 2. Environment of conserved amino acis surrounding the site of phosphotransfer. For this diagram a serine (shown in red) was modeled into the P site so that distances between the "y-phosphate and a protein substrate could be estimated. The primary metal site, OM382, is coordinated by the invariant Asp184, as well as two water molecules as indicated above. The secondary inhibitory metal site, OM383, is coordiated by the invariant Asnl7, by invariant Asp184, as well as by one water molecule. Asp14, therefore, is shared by both metal sites in this inhibited complex.

The above figure is reproduced from the cited reference with permission from the IUCr

Secondary reference #4

• 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 #5

• 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

Secondary reference #6

• Title: Expression of the catalytic subunit of camp-Dependent protein kinase in escherichia coli.
• Authors: L.W.Slice, S.S.Taylor.
• Ref.: J Biol Chem, 1989, 264, 20940-20946.
• PubMed id: 2687267