1993
DOI: 10.1002/j.1460-2075.1993.tb05725.x
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Phosphotransferase and substrate binding mechanism of the cAMP-dependent protein kinase catalytic subunit from porcine heart as deduced from the 2.0 A structure of the complex with Mn2+ adenylyl imidodiphosphate and inhibitor peptide PKI(5-24).

Abstract: The crystal structure of the porcine heart catalytic subunit of cAMP‐dependent protein kinase in a ternary complex with the MgATP analogue MnAMP‐PNP and a pseudosubstrate inhibitor peptide, PKI(5‐24), has been solved at 2.0 A resolution from monoclinic crystals of the catalytic subunit isoform CA. The refinement is presently at an R factor of 0.194 and the active site of the molecule is well defined. The glycine‐rich phosphate anchor of the nucleotide binding fold motif of the protein kinase is a beta ribbon a… Show more

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Cited by 391 publications
(462 citation statements)
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References 80 publications
(55 reference statements)
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“…Usually, such non-proline cis-peptides are found close to the active site or catalytic center of an enzyme. This is obviously the case here, because the glycinerich loop frames the border of the active site and participates in binding and orienting the triphosphoryl group of ATP (33). These new glycine flap orientations, especially those of groups two and three, have not been observed previously.…”
Section: Overall Structuresupporting
confidence: 61%
See 1 more Smart Citation
“…Usually, such non-proline cis-peptides are found close to the active site or catalytic center of an enzyme. This is obviously the case here, because the glycinerich loop frames the border of the active site and participates in binding and orienting the triphosphoryl group of ATP (33). These new glycine flap orientations, especially those of groups two and three, have not been observed previously.…”
Section: Overall Structuresupporting
confidence: 61%
“…It binds not only to the 3ЈOH-group of ATP but has an important role in recognition of the substrate consensus sequence of PKA (33,34). Glu-127 interacts with Arg-2 (Arg-18 in PKI(5-24)) of the substrate recognition sequence RRX(S/ T)Y. Asp-127, conserved in most AGC kinases, and in many others, is a true homologue of Glu-127 in this respect, because it makes a bidentate contact to the guanidinium group of Arg-18 from the bound PKI(5-24) pseudosubstrate peptide.…”
Section: Effect Of the Mutations On Y-27632mentioning
confidence: 99%
“…The star-stop positions of the secondary structures are noted at the right of the segments according to the X-ray crystallographic data (Bossemeyer et al, 1993;Eriksson et al, 1997;Fan et al, 1997). Positions of equivalent residues forming hydrogen bonds and hydrophobic interactions with the cofactors are marked by "*" and ''n ," respectively.…”
Section: Resultsmentioning
confidence: 99%
“…These last two fold classes are particularly interesting. Although the folds are different, two of their typical members, CAMP-dependent protein kinase (cAPK) from the one family (Bossemeyer et al, 1993) and D-Ala:D-Ala ligase (m-ligase) from the other family (Fan et al, 1994(Fan et al, , 1997, have over 100 structurally-equivalent residues from ten segments that form two identical supersecondary structures between which the cofactor ATP is bound in a similar way (Denessiouk et al, 1998).…”
mentioning
confidence: 99%
“…A similar observation on the lack of interaction between the bound ATP or AMP-PNP molecule and the P-loop was reported in the crystal structure of insulin receptor tyrosine kinase (IRK) [10] (Supplementary information, Figure S6D). By contrast, the P-loops of the cAMP-dependent protein kinase (cAPK) (Supplementary information, Figure S6B) and the γ-subunit of phosphorylase kinase (PHK) (Supplementary information, Figure S6C) significantly contribute to the stabilization of the β-and γ-phosphates of ATP [11]. This phenomenon indicates the variations in the stabilization of ATP binding by the P-loop of different kinase family members.…”
Section: Dear Editormentioning
confidence: 99%