'''Crystal Structure of the Catalytic Subunit of cAMP-dependent Protein Kinase Complexed with a Phosphorylated Substrate Peptide and Detergent'''
===Crystal Structure of the Catalytic Subunit of cAMP-dependent Protein Kinase Complexed with a Phosphorylated Substrate Peptide and Detergent===
==Overview==
<!--
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.
The line below this paragraph, {{ABSTRACT_PUBMED_8003955}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 8003955 is the PubMed ID number.
-->
{{ABSTRACT_PUBMED_8003955}}
==About this Structure==
==About this Structure==
Line 31:
Line 35:
[[Category: Xuong, N H.]]
[[Category: Xuong, N H.]]
[[Category: Protein kinase-phosphorylated substrate complex]]
[[Category: Protein kinase-phosphorylated substrate complex]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 21:22:55 2008''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 20:26:46 2008''
Revision as of 20:26, 1 July 2008
This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.
Crystal Structure of the Catalytic Subunit of cAMP-dependent Protein Kinase Complexed with a Phosphorylated Substrate Peptide and DetergentCrystal Structure of the Catalytic Subunit of cAMP-dependent Protein Kinase Complexed with a Phosphorylated Substrate Peptide and Detergent
1JLU is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
cAMP-dependent protein kinase: crystallographic insights into substrate recognition and phosphotransfer., Madhusudan, Trafny EA, Xuong NH, Adams JA, Ten Eyck LF, Taylor SS, Sowadski JM, Protein Sci. 1994 Feb;3(2):176-87. PMID:8003955
