The entry DI1010103 describes the same interaction with the disordered partner bearing different post-translational modification(s).
Database Accession: DI1010105
Name: cAMP-dependent protein kinase catalytic subunit in complex with phosphorylated cAMP-dependent protein kinase inhibitor
PDB ID: 1jlu
Experimental method: X-ray (2.25 Å)
Source organism: Homo sapiens / Mus musculus
Proof of disorder:
Primary publication of the structure:
Trafny EA, Xuong NH, Adams JA, Ten Eyck LF, Taylor SS, Sowadski JM
cAMP-dependent protein kinase: crystallographic insights into substrate recognition and phosphotransfer.
(1994) Protein Sci. 3: 176-87
PMID: 8003955
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.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
protein kinase binding Interacting selectively and non-covalently with a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein kinase A binding Interacting selectively and non-covalently with any subunit of protein kinase A.
Biological process:
regulation of intracellular protein transport Any process that modulates the frequency, rate or extent of the directed movement of proteins within cells.
Cellular component:
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: S, E
Notes: No modifications of the original PDB file.
Name: cAMP-dependent protein kinase inhibitor alpha
Source organism: Homo sapiens
Length: 20 residues
Sequence:Sequence according to PDB SEQRESTTYADFIASGRTGRRASIHD
The sequence contains the following modified/non-standard residues:
• phosphoserine (S) at position 22 (PDB position: 377)
UniProtKB AC: P61925 (positions: 6-25) Coverage: 26.3%
UniRef90 AC: UniRef90_P61925 (positions: 6-25)
Name: cAMP-dependent protein kinase catalytic subunit alpha
Source organism: Mus musculus
Length: 350 residues
Sequence:Sequence according to PDB SEQRESGNAAAAKKGSEQESVKEFLAKAKEDFLKKWETPSQNTAQLDQFDRIKTLGTGSFGRVMLVKHKESGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEYVAGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSLDLIYRDLKPENLLIDQQGYIQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSSDLKDLLRNLLQVDLTKRFGNLKNGVNDIKNHKWFATTDWIAIYQRKVEAPFIPKFKGPGDTSNFDDYEEEEIRVSINEKCGKEFTEF
UniProtKB AC: P05132 (positions: 2-351) Coverage: 99.7%
UniRef90 AC: UniRef90_P17612 (positions: 2-351)
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Chain S:
The 1-76 region described in DisProt entry DP00015 and the 1-32 region describen in IDEAL entry IID00349 cover 100% of the binding sequence in a homologous protein.
Chain E:
The protein kinase domain involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF00069). A solved monomeric structure of the domain is represented by PDB ID 1i09.
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). The structure can be rotated by left click and hold anywhere on the structure. Representation options can be edited by right clicking on the structure window.
