Stereochemical and kinetic studies on the action of the catalytic subunit of bovine cardiac muscle adenosine 3',5'-monophosphate dependent protein kinase using metal ion complexes of ATP.beta.S

Dw, Bolen; J, Stingelin; Hn, Bramson; Et, Kaiser

doi:10.1021/bi00547a022

Cited by 28 publications

(20 citation statements)

References 20 publications

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“…The ribose has an unsymmetrical twist with major 3' endo and minor 2' exo puckering. MnAMP-PNP in the crystal structure is bound as the D stereoisomer, which is the preferred ,B -y bidentate metal ATP complex for the catalytic subunit Bolen et al, 1980). To our knowledge, no other high resolution structure of an enzyme bound Mn or MgATP complex has been determined.…”

Section: The Nucleotide Foldmentioning

confidence: 98%

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).

et al. 1993

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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 acting as a flap with conformational flexibility over the triphosphate group. The glycines seem to be conserved to avoid steric clash with ATP. The known synergistic effects of substrate binding can be explained by hydrogen bonds present only in the ternary complex. Implications for the kinetic scheme of binding order are discussed. The structure is assumed to represent a phosphotransfer competent conformation. The invariant conserved residue Asp166 is proposed to be the catalytic base and Lys168 to stabilize the transition state. In some tyrosine kinases Lys168 is functionally replaced by an Arg displaced by two residues in the primary sequence, suggesting invariance in three‐dimensional space. The structure supports an in‐line transfer with a pentacoordinate transition state at the phosphorus with very few nuclear movements.

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Section: The Nucleotide Foldmentioning

confidence: 98%

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).

et al. 1993

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“…66 Jaffe and Cohn have shown from 31P NMR studies that Cd(I1) chelates ATPpS and ATPyS through the sulfur atom while Mg(I1) chelates the same ATP analogs through the oxygen atom of the thiophosphoryl Because of these metal ion preferences, P,y-bidentate MgATPPS "A" and P,y-bidentate CdATPpS "B" are expected to be geometrically equivalent,67 as shown in Figure 4. Unlike MgATP the complexes of Co(NH,),ATP are substitution-inert, and the stereoisomers are, therefore, separable.…”

Section: B Stereochemistry Of the Reactive Metal-ion-nucleoside-tripmentioning

confidence: 99%

Mechanistic Studies of cAMP-Dependent Protein Kinase Action

Bramson

Kaiser

Mildvan

et al. 1984

Critical Reviews in Biochemistry

113

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“…Protein kinase C possesses no activity with Cd'+ as the activating metal. This behavior is also different from that of protein kinase A [2].…”

Section: Resultsmentioning

confidence: 56%

“…As shown in table 1, both isomers exhibited almost identical reactivity, which is about 15% that of ATP. This result is in sharp contrast to that for protein kinase A, which adopts the SP isomer as the preferred substrate by a large margin [2]. To rule out the possibility that the data on protein kinase C are due to an artifact of our ATP,&S preparations, stereochemical studies were also carried out for protein kinase A.…”

Section: Resultsmentioning

confidence: 76%

“…Despite such biological importance, little is known about the mechanism by which these enzymes mediate the phosphoryl transfer to an acceptor substrate. Bolen and collaborators [2] reported that CAMP-dependent protein kinase (protein kinase A) exhibits high stereospecificity for the A configuration of Mg-ATP as substrate. An intriguing question is raised as to whether other protein kinases show the same stereospecificity.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Configuration of the active Mg‐ATP complex in protein kinase C reaction

et al. 1986

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To probe the active site structure of protein kinase C stereochemical studies were carried out by using ATPBS. The enzyme utilizes either one of the diastereomers (Sr and RP) of ATPj?S almost equally well as a substrate. This result contrasts with that for cyclic AMP-dependent protein kinase, suggesting that the topography of the nucleotide-binding site is significantly different between the two kinases. Phosphorylation Protein kinase C ATP/?S Stereospecijicity

show abstract

Stereochemical and kinetic studies on the action of the catalytic subunit of bovine cardiac muscle adenosine 3',5'-monophosphate dependent protein kinase using metal ion complexes of ATP.beta.S

Cited by 28 publications

References 20 publications

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).

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).

Mechanistic Studies of cAMP-Dependent Protein Kinase Action

Configuration of the active Mg‐ATP complex in protein kinase C reaction

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