1j2m: Difference between revisions

Revision as of 19:06, 25 December 2014

Solution structure of CPI-17(22-120)

Structural highlights

1j2m is a 1 chain structure with sequence from Sus scrofa. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1j2n
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[PP14A_PIG] Inhibitor of PPP1CA. Has over 1000-fold higher inhibitory activity when phosphorylated, creating a molecular switch for regulating the phosphorylation status of PPP1CA substrates and smooth muscle contraction.^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

We present solution NMR structures for wild-type and mutated forms of CPI-17, a phosphoinhibitor for protein phosphatase 1. Phosphorylation of Thr38 of CPI-17 produces a >1000-fold increase in inhibitory potency for myosin phosphatase. We compared the 1H-15N heteronuclear single quantum coherence spectroscopy (HSQC) chemical shifts of wild-type CPI-17, partially phosphorylated CPI-17 and CPI-17 with Thr38 replaced with Asp to introduce a negative charge. There was a switch in the protein conformation due to either Asp substitution or phosphorylation, so we determined the solution NMR structure of the CPI-17 T38D mutant as a model for the active (phospho-) conformation. The structures reveal a molecular switch in conformation that involves the rotation of two of the four helices in the four helix bundle. Despite this conformational switch, there was little increase in the inhibitory potency with T38D. We propose that for this inhibitor, a negative charge at residue 38 is sufficient to trigger an active conformation, but a phosphoryl group is required for full inhibitory potency against protein phosphatase-1.

Distinctive solution conformation of phosphatase inhibitor CPI-17 substituted with aspartate at the phosphorylation-site threonine residue.,Ohki S, Eto M, Shimizu M, Takada R, Brautigan DL, Kainosho M J Mol Biol. 2003 Mar 7;326(5):1539-47. PMID:12595264^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Eto M, Senba S, Morita F, Yazawa M. Molecular cloning of a novel phosphorylation-dependent inhibitory protein of protein phosphatase-1 (CPI17) in smooth muscle: its specific localization in smooth muscle. FEBS Lett. 1997 Jun 30;410(2-3):356-60. PMID:9237662
↑ Eto M, Ohmori T, Suzuki M, Furuya K, Morita F. A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media and characterization. J Biochem. 1995 Dec;118(6):1104-7. PMID:8720121
↑ Hamaguchi T, Ito M, Feng J, Seko T, Koyama M, Machida H, Takase K, Amano M, Kaibuchi K, Hartshorne DJ, Nakano T. Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N. Biochem Biophys Res Commun. 2000 Aug 11;274(3):825-30. PMID:10924361 doi:https://dx.doi.org/10.1006/bbrc.2000.3225
↑ Koyama M, Ito M, Feng J, Seko T, Shiraki K, Takase K, Hartshorne DJ, Nakano T. Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase. FEBS Lett. 2000 Jun 23;475(3):197-200. PMID:10869555
↑ Ohki S, Eto M, Shimizu M, Takada R, Brautigan DL, Kainosho M. Distinctive solution conformation of phosphatase inhibitor CPI-17 substituted with aspartate at the phosphorylation-site threonine residue. J Mol Biol. 2003 Mar 7;326(5):1539-47. PMID:12595264

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Eto M, Senba S, Morita F, Yazawa M. Molecular cloning of a novel phosphorylation-dependent inhibitory protein of protein phosphatase-1 (CPI17) in smooth muscle: its specific localization in smooth muscle. FEBS Lett. 1997 Jun 30;410(2-3):356-60. PMID:9237662

[2] Eto M, Ohmori T, Suzuki M, Furuya K, Morita F. A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media and characterization. J Biochem. 1995 Dec;118(6):1104-7. PMID:8720121

[3] Hamaguchi T, Ito M, Feng J, Seko T, Koyama M, Machida H, Takase K, Amano M, Kaibuchi K, Hartshorne DJ, Nakano T. Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N. Biochem Biophys Res Commun. 2000 Aug 11;274(3):825-30. PMID:10924361 doi:https://dx.doi.org/10.1006/bbrc.2000.3225

[4] Koyama M, Ito M, Feng J, Seko T, Shiraki K, Takase K, Hartshorne DJ, Nakano T. Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase. FEBS Lett. 2000 Jun 23;475(3):197-200. PMID:10869555

[5] Ohki S, Eto M, Shimizu M, Takada R, Brautigan DL, Kainosho M. Distinctive solution conformation of phosphatase inhibitor CPI-17 substituted with aspartate at the phosphorylation-site threonine residue. J Mol Biol. 2003 Mar 7;326(5):1539-47. PMID:12595264

[1]

[2]

[3]

[4]

[5]

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1j2m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J2M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1J2M FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1j2n|1j2n]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1j2n|1j2n]]</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1j2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j2m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1j2m RCSB], [http://www.ebi.ac.uk/pdbsum/1j2m PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1j2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j2m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1j2m RCSB], [http://www.ebi.ac.uk/pdbsum/1j2m PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/PP14A_PIG PP14A_PIG]] Inhibitor of PPP1CA. Has over 1000-fold higher inhibitory activity when phosphorylated, creating a molecular switch for regulating the phosphorylation status of PPP1CA substrates and smooth muscle contraction.<ref>PMID:9237662</ref> <ref>PMID:8720121</ref> <ref>PMID:10924361</ref> <ref>PMID:10869555</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 29: / Line 31: @@
 </StructureSection>
 [[Category: Sus scrofa]]
-[[Category: Brautigan, D L.]]
+[[Category: Brautigan, D L]]
-[[Category: Eto, M.]]
+[[Category: Eto, M]]
-[[Category: Kainosho, M.]]
+[[Category: Kainosho, M]]
-[[Category: Ohki, S.]]
+[[Category: Ohki, S]]
-[[Category: Shimizu, M.]]
+[[Category: Shimizu, M]]
-[[Category: Takada, R.]]
+[[Category: Takada, R]]
 [[Category: Helix bundle]]
 [[Category: Protein binding]]

1j2m: Difference between revisions

Revision as of 19:06, 25 December 2014

Solution structure of CPI-17(22-120)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

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