PDBsum entry 1l3r

Transferase

PDB id: 1l3r

Contents

Protein chains

341 a.a. *

20 a.a. *

Ligands

ADP-AF3

MPD

Metals

_MG ×2

Waters ×233

* Residue conservation analysis

PDB id:

1l3r

Name:

Transferase

Title:

Crystal structure of a transition state mimic of the catalytic subunit of camp-dependent protein kinase

Structure:

Camp-dependent protein kinase, alpha-catalytic subunit. Chain: e. Synonym: pka c-alpha. Engineered: yes. Camp-dependent protein kinase inhibitor, muscle/brain form. Chain: i. Fragment: residues 5-24. Synonym: pki-alpha. Engineered: yes.

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence of the peptide is naturally found in mus musculus (mouse).

Biol. unit:

Dimer (from PQS)

Resolution:

2.00Å R-factor: 0.205 R-free: 0.232

Authors:

Madhusudan,P.Akamine,N.-H.Xuong,S.S.Taylor

Key ref:

Madhusudan et al. (2002). Crystal structure of a transition state mimic of the catalytic subunit of cAMP-dependent protein kinase. Nat Struct Biol, 9, 273-277. PubMed id: 11896404 DOI: 10.1038/nsb780

Date:

28-Feb-02 Release date: 20-Mar-02

Protein chain

P05132  (KAPCA_MOUSE) -  cAMP-dependent protein kinase catalytic subunit alpha from Mus musculus

Seq: 351 a.a.

Struc: 341 a.a.*

Protein chain

P63249  (IPKA_RAT) -  cAMP-dependent protein kinase inhibitor alpha from Rattus norvegicus

Seq: 76 a.a.

Struc: 20 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain E: E.C.2.7.11.11 - cAMP-dependent 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⁺

L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] (Bound ligand (Het Group name = ADP) corresponds exactly) + ADP + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] (Bound ligand (Het Group name = ADP) corresponds exactly) + ADP + H(+)

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

reference

DOI no: 10.1038/nsb780

Nat Struct Biol 9:273-277 (2002)

PubMed id: 11896404

Crystal structure of a transition state mimic of the catalytic subunit of cAMP-dependent protein kinase.

Madhusudan, P.Akamine, N.H.Xuong, S.S.Taylor.

ABSTRACT

To understand the molecular mechanism underlying phosphoryl transfer of cAMP-dependent protein kinase, the structure of the catalytic subunit in complex with ADP, aluminum fluoride, Mg2+ ions and a substrate peptide was determined at 2.0 A resolution. Aluminum fluoride was modeled as AlF3 in a planar geometry; it is positioned 2.3 A from both the donor oxygen of ADP and the hydroxyl group of the recipient Ser residue. In this configuration, the aluminum atom forms a trigonal bipyramidal coordination with the oxygen atoms of the donor and recipient groups at the apical positions. This arrangement suggests that aluminum fluoride mimics the transition state and provides the first direct structural evidence for the in-line mechanism of phosphoryl transfer in a protein kinase.

Selected figure(s)

Figure 1.
Figure 1. Overall view of the Mg[2]ADP -SP20 -AlF[3] complex of the catalytic subunit (cAPK) with the difference density at the position of AlF[3]. a, The disordered region of the catalytic subunit consisting of residues 5 -13 is indicated by dashes. SP20 and Mg2+ ions are displayed in yellow and red, respectively, and ADP and AlF[3] are shown in green. The Gly-rich loop is colored in magenta, and black spheres indicate the three phosphorylation sites observed in the structure. The MPD molecule is displayed in cyan. This figure was generated using MOLSCRIPT33. b, Stereo view of the annealed F[o] - F[c] omit map contoured at 6.0 . This figure was generated from BOBSCRIPT33, 34. Dashed lines indicate the aluminum (Al) coordination with the -phosphate of ADP and the hydroxyl group of Ser from the SP20.

Figure 3.
Figure 3. Schematic representation depicting the detailed interactions of aluminum fluoride with Mg[2]ADP, active site residues of the catalytic subunit, water molecules and the phosphorylation site Ser from SP20. Mg2+ ions and water molecules are indicated in large and small spheres, respectively. Residues displayed in ball-and-stick representation exhibit the exact conformation and relative orientation as observed in the crystal structure; however, they have been displaced with respect to one another for clarity.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 273-277) copyright 2002.

Figures were selected by an automated process.