PDBsum entry 1smh

Signaling protein,transferase/inhibitor

PDB id: 1smh

Contents

Protein chains

350 a.a. *

20 a.a. *

Ligands

BU3 ×6

MG8

Waters ×175

* Residue conservation analysis

PDB id:

1smh

Name:

Signaling protein,transferase/inhibitor

Title:

Protein kinase a variant complex with completely ordered n-terminal helix

Structure:

Camp-dependent protein kinase, alpha-catalytic subunit. Chain: a. Fragment: catalytic subunit. Synonym: pka c-alpha. Engineered: yes. Mutation: yes. Camp-dependent protein kinase inhibitor, alpha form. Chain: b. Fragment: residues 5-24.

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Gene: prkaca. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: peptide synthesis. This sequence occurs naturally in humans

Biol. unit:

Dimer (from PQS)

Resolution:

2.04Å R-factor: 0.191 R-free: 0.238

Authors:

C.Breitenlechner,R.A.Engh,R.Huber,V.Kinzel,D.Bossemeyer,M.Gassel

Key ref:

C.Breitenlechner et al. (2004). The typically disordered N-terminus of PKA can fold as a helix and project the myristoylation site into solution. Biochemistry, 43, 7743-7749. PubMed id: 15196017 DOI: 10.1021/bi0362525

Date:

09-Mar-04 Release date: 06-Jul-04

Protein chain

P00517  (KAPCA_BOVIN) -  cAMP-dependent protein kinase catalytic subunit alpha from Bos taurus

Seq: 351 a.a.

Struc: 350 a.a.*

Protein chain

P61926  (IPKA_RABIT) -  cAMP-dependent protein kinase inhibitor alpha from Oryctolagus cuniculus

Seq: 76 a.a.

Struc: 20 a.a.

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain A: 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⁺

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

reference

DOI no: 10.1021/bi0362525

Biochemistry 43:7743-7749 (2004)

PubMed id: 15196017

The typically disordered N-terminus of PKA can fold as a helix and project the myristoylation site into solution.

C.Breitenlechner, R.A.Engh, R.Huber, V.Kinzel, D.Bossemeyer, M.Gassel.

ABSTRACT

Protein kinases comprise the major enzyme family critically involved in signal transduction pathways; posttranslational modifications affect their regulation and determine signaling states. The prototype protein kinase A (PKA) possesses an N-terminal alpha-helix (Helix A) that is atypical for kinases and is thus a major distinguishing feature of PKA. Its physiological function may involve myristoylation at the N-terminus and modulation via phosphorylation at serine 10. Here we describe an unusual structure of an unmyristoylated PKA, unphosphorylated at serine 10, with a completely ordered N-terminus. Using standard conditions (e.g., PKI 5-24, ATP site ligand, MEGA-8), a novel 2-fold phosphorylated PKA variant showed the ordered N-terminus in a new crystal packing arrangement. Thus, the critical factor for structuring the N-terminus is apparently the absence of phosphorylation of Ser10. The flexibility of the N-terminus, its myristoylation, and the conformational dependence on the phosphorylation state are consistent with a functional role for myristoylation.