1JBP

Crystal Structure of the Catalytic Subunit of cAMP-dependent Protein Kinase Complexed with a Substrate Peptide, ADP and Detergent


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Observed: 0.175 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

cAMP-dependent protein kinase: crystallographic insights into substrate recognition and phosphotransfer.

MadhusudanTrafny, E.A.Xuong, N.H.Adams, J.A.Ten Eyck, L.F.Taylor, S.S.Sowadski, J.M.

(1994) Protein Sci 3: 176-187

  • DOI: https://doi.org/10.1002/pro.5560030203
  • Primary Citation of Related Structures:  
    1JBP, 1JLU

  • PubMed Abstract: 

    The crystal structure of ternary and binary substrate complexes of the catalytic subunit of cAMP-dependent protein kinase has been refined at 2.2 and 2.25 A resolution, respectively. The ternary complex contains ADP and a 20-residue substrate peptide, whereas the binary complex contains the phosphorylated substrate peptide. These 2 structures were refined to crystallographic R-factors of 17.5 and 18.1%, respectively. In the ternary complex, the hydroxyl oxygen OG of the serine at the P-site is 2.7 A from the OD1 atom of Asp 166. This is the first crystallographic evidence showing the direct interaction of this invariant carboxylate with a peptide substrate, and supports the predicted role of Asp 166 as a catalytic base and as an agent to position the serine -OH for nucleophilic attack. A comparison of the substrate and inhibitor ternary complexes places the hydroxyl oxygen of the serine 2.7 A from the gamma-phosphate of ATP and supports a direct in-line mechanism for phosphotransfer. In the binary complex, the phosphate on the Ser interacts directly with the epsilon N of Lys 168, another conserved residue. In the ternary complex containing ATP and the inhibitor peptide, Lys 168 interacts electrostatically with the gamma-phosphate of ATP (Zheng J, Knighton DR, Ten Eyck LF, Karlsson R, Xuong NH, Taylor SS, Sowadski JM, 1993, Biochemistry 32:2154-2161). Thus, Lys 168 remains closely associated with the phosphate in both complexes. A comparison of this binary complex structure with the recently solved structure of the ternary complex containing ATP and inhibitor peptide also reveals that the phosphate atom traverses a distance of about 1.5 A following nucleophilic attack by serine and transfer to the peptide. No major conformational changes of active site residues are seen when the substrate and product complexes are compared, although the binary complex with the phosphopeptide reveals localized changes in conformation in the region corresponding to the glycine-rich loop. The high B-factors for this loop support the conclusion that this structural motif is a highly mobile segment of the protein.


  • Organizational Affiliation

    Department of Medicine, University of California at San Diego, La Jolla 92093-0654.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CAMP-DEPENDENT PROTEIN KINASE, ALPHA-CATALYTIC SUBUNITA [auth E]350Mus musculusMutation(s): 3 
EC: 2.7.1.37
UniProt
Find proteins for P05132 (Mus musculus)
Explore P05132 
Go to UniProtKB:  P05132
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP05132
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
CAMP-DEPENDENT PROTEIN KINASE INHIBITOR, MUSCLE/BRAIN FORMB [auth S]20N/AMutation(s): 2 
UniProt
Find proteins for P61926 (Oryctolagus cuniculus)
Explore P61926 
Go to UniProtKB:  P61926
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP61926
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ADP
Query on ADP

Download Ideal Coordinates CCD File 
C [auth E]ADENOSINE-5'-DIPHOSPHATE
C10 H15 N5 O10 P2
XTWYTFMLZFPYCI-KQYNXXCUSA-N
OCT
Query on OCT

Download Ideal Coordinates CCD File 
D [auth E]N-OCTANE
C8 H18
TVMXDCGIABBOFY-UHFFFAOYSA-N
Modified Residues  2 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
A [auth E]L-PEPTIDE LINKINGC3 H8 N O6 PSER
TPO
Query on TPO
A [auth E]L-PEPTIDE LINKINGC4 H10 N O6 PTHR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Observed: 0.175 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 73.96α = 90
b = 76.11β = 90
c = 81γ = 90
Software Package:
Software NamePurpose
X-PLORmodel building
TNTrefinement
UCSD-systemdata reduction
UCSD-systemdata scaling
X-PLORphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-06-27
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-04
    Changes: Refinement description
  • Version 1.4: 2021-10-27
    Changes: Database references, Derived calculations
  • Version 1.5: 2023-08-16
    Changes: Data collection, Refinement description