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New page: left|200px<br /><applet load="1k5o" size="450" color="white" frame="true" align="right" spinBox="true" caption="1k5o" /> '''CPI-17(35-120) deletion mutant'''<br /> ==O...
 
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[[Image:1k5o.gif|left|200px]]<br /><applet load="1k5o" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1k5o" />
'''CPI-17(35-120) deletion mutant'''<br />


==Overview==
==CPI-17(35-120) deletion mutant==
Contractility of vascular smooth muscle depends on phosphorylation of, myosin light chains, and is modulated by hormonal control of myosin, phosphatase activity. Signaling pathways activate kinases such as PKC or, Rho-dependent kinases that phosphorylate the myosin phosphatase inhibitor, protein called CPI-17. Phosphorylation of CPI-17 at Thr38 enhances its, inhibitory potency 1000-fold, creating a molecular on/off switch for, regulating contraction. We report the solution NMR structure of the CPI-17, inhibitory domain (residues 35-120), which retains the signature, biological properties of the full-length protein. The final ensemble of 20, sets of NMR coordinates overlaid onto their mean structure with r.m.s.d., values of 0.84(+/-0.22) A for the backbone atoms. The protein forms a, novel four-helix, V-shaped bundle comprised of a central anti-parallel, helix pair (B/C helices) flanked by two large spiral loops formed by the N, and C termini that are held together by another anti-parallel helix pair, (A/D helices) stabilized by intercalated aromatic and aliphatic, side-chains. Chemical shift perturbations indicated that phosphorylation, of Thr38 induces a conformational change involving displacement of helix, A, without significant movement of the other three helices. This, conformational change seems to flex one arm of the molecule, thereby, exposing new surfaces of the helix A and the nearby phosphorylation loop, to form specific interactions with the catalytic site of the phosphatase., This phosphorylation-dependent conformational change offers new structural, insights toward understanding the specificity of CPI-17 for myosin, phosphatase and its function as a molecular switch.
<StructureSection load='1k5o' size='340' side='right'caption='[[1k5o]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1k5o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K5O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1K5O FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1k5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k5o OCA], [https://pdbe.org/1k5o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1k5o RCSB], [https://www.ebi.ac.uk/pdbsum/1k5o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1k5o ProSAT]</span></td></tr>
</table>
== Function ==
[https://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]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k5/1k5o_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1k5o ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Contractility of vascular smooth muscle depends on phosphorylation of myosin light chains, and is modulated by hormonal control of myosin phosphatase activity. Signaling pathways activate kinases such as PKC or Rho-dependent kinases that phosphorylate the myosin phosphatase inhibitor protein called CPI-17. Phosphorylation of CPI-17 at Thr38 enhances its inhibitory potency 1000-fold, creating a molecular on/off switch for regulating contraction. We report the solution NMR structure of the CPI-17 inhibitory domain (residues 35-120), which retains the signature biological properties of the full-length protein. The final ensemble of 20 sets of NMR coordinates overlaid onto their mean structure with r.m.s.d. values of 0.84(+/-0.22) A for the backbone atoms. The protein forms a novel four-helix, V-shaped bundle comprised of a central anti-parallel helix pair (B/C helices) flanked by two large spiral loops formed by the N and C termini that are held together by another anti-parallel helix pair (A/D helices) stabilized by intercalated aromatic and aliphatic side-chains. Chemical shift perturbations indicated that phosphorylation of Thr38 induces a conformational change involving displacement of helix A, without significant movement of the other three helices. This conformational change seems to flex one arm of the molecule, thereby exposing new surfaces of the helix A and the nearby phosphorylation loop to form specific interactions with the catalytic site of the phosphatase. This phosphorylation-dependent conformational change offers new structural insights toward understanding the specificity of CPI-17 for myosin phosphatase and its function as a molecular switch.


==About this Structure==
Solution NMR structure of the myosin phosphatase inhibitor protein CPI-17 shows phosphorylation-induced conformational changes responsible for activation.,Ohki S, Eto M, Kariya E, Hayano T, Hayashi Y, Yazawa M, Brautigan D, Kainosho M J Mol Biol. 2001 Dec 7;314(4):839-49. PMID:11734001<ref>PMID:11734001</ref>
1K5O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1K5O OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Solution NMR structure of the myosin phosphatase inhibitor protein CPI-17 shows phosphorylation-induced conformational changes responsible for activation., Ohki S, Eto M, Kariya E, Hayano T, Hayashi Y, Yazawa M, Brautigan D, Kainosho M, J Mol Biol. 2001 Dec 7;314(4):839-49. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11734001 11734001]
</div>
[[Category: Single protein]]
<div class="pdbe-citations 1k5o" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Sus scrofa]]
[[Category: Brautigan, D.]]
[[Category: Brautigan D]]
[[Category: Eto, M.]]
[[Category: Eto M]]
[[Category: Hayano, T.]]
[[Category: Hayano T]]
[[Category: Hayashi, Y.]]
[[Category: Hayashi Y]]
[[Category: Kainosho, M.]]
[[Category: Kainosho M]]
[[Category: Kariya, E.]]
[[Category: Kariya E]]
[[Category: Ohki, S.]]
[[Category: Ohki S]]
[[Category: Yazawa, M.]]
[[Category: Yazawa M]]
[[Category: mlcp-inhibitor]]
[[Category: phosphorylation]]
[[Category: pp1-inhibitor]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 18:52:35 2007''

Latest revision as of 21:12, 29 May 2024

CPI-17(35-120) deletion mutantCPI-17(35-120) deletion mutant

Structural highlights

1k5o 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.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Contractility of vascular smooth muscle depends on phosphorylation of myosin light chains, and is modulated by hormonal control of myosin phosphatase activity. Signaling pathways activate kinases such as PKC or Rho-dependent kinases that phosphorylate the myosin phosphatase inhibitor protein called CPI-17. Phosphorylation of CPI-17 at Thr38 enhances its inhibitory potency 1000-fold, creating a molecular on/off switch for regulating contraction. We report the solution NMR structure of the CPI-17 inhibitory domain (residues 35-120), which retains the signature biological properties of the full-length protein. The final ensemble of 20 sets of NMR coordinates overlaid onto their mean structure with r.m.s.d. values of 0.84(+/-0.22) A for the backbone atoms. The protein forms a novel four-helix, V-shaped bundle comprised of a central anti-parallel helix pair (B/C helices) flanked by two large spiral loops formed by the N and C termini that are held together by another anti-parallel helix pair (A/D helices) stabilized by intercalated aromatic and aliphatic side-chains. Chemical shift perturbations indicated that phosphorylation of Thr38 induces a conformational change involving displacement of helix A, without significant movement of the other three helices. This conformational change seems to flex one arm of the molecule, thereby exposing new surfaces of the helix A and the nearby phosphorylation loop to form specific interactions with the catalytic site of the phosphatase. This phosphorylation-dependent conformational change offers new structural insights toward understanding the specificity of CPI-17 for myosin phosphatase and its function as a molecular switch.

Solution NMR structure of the myosin phosphatase inhibitor protein CPI-17 shows phosphorylation-induced conformational changes responsible for activation.,Ohki S, Eto M, Kariya E, Hayano T, Hayashi Y, Yazawa M, Brautigan D, Kainosho M J Mol Biol. 2001 Dec 7;314(4):839-49. PMID:11734001[5]

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

References

  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:http://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, Kariya E, Hayano T, Hayashi Y, Yazawa M, Brautigan D, Kainosho M. Solution NMR structure of the myosin phosphatase inhibitor protein CPI-17 shows phosphorylation-induced conformational changes responsible for activation. J Mol Biol. 2001 Dec 7;314(4):839-49. PMID:11734001 doi:http://dx.doi.org/10.1006/jmbi.2001.5200
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