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PDBsum entry 5c1v
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PDB id:
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Hydrolase
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Title:
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Crystal structure analysis of catalytic subunit of human calcineurin
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Structure:
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Serine/threonine-protein phosphatase 2b catalytic subunit alpha isoform. Chain: a, b. Fragment: catalytic domain, residues 2-347. Synonym: cam-prp catalytic subunit,calmodulin-dependent calcineurin a subunit alpha isoform. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: ppp3ca, calna, cna. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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3.35Å
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R-factor:
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0.217
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R-free:
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0.249
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Authors:
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A.Guasch,I.Fita,R.Perez-Luque,D.Aparicio,A.Aranguren-Ibanez,M.Perez- Riba
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Key ref:
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A.Guasch
et al.
(2015).
Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization.
Plos One,
10,
e0134569.
PubMed id:
DOI:
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Date:
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15-Jun-15
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Release date:
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03-Feb-16
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PROCHECK
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Headers
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References
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Q08209
(PP2BA_HUMAN) -
Protein phosphatase 3 catalytic subunit alpha from Homo sapiens
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Seq:
Struc:
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521 a.a.
317 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.3.1.3.16
- protein-serine/threonine phosphatase.
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Reaction:
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1.
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O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate
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2.
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O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate
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O-phospho-L-seryl-[protein]
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+
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H2O
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=
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L-seryl-[protein]
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+
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phosphate
Bound ligand (Het Group name = )
corresponds exactly
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O-phospho-L-threonyl-[protein]
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+
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H2O
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=
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L-threonyl-[protein]
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+
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phosphate
Bound ligand (Het Group name = )
corresponds exactly
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Plos One
10:e0134569
(2015)
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PubMed id:
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Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization.
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A.Guasch,
..Aranguren-Ibáñez,
R.Pérez-Luque,
D.Aparicio,
S.Martínez-Høyer,
M.C.Mulero,
E.Serrano-Candelas,
M.Pérez-Riba,
I.Fita.
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ABSTRACT
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A limited repertoire of PPP family of serine/threonine phosphatases with a
highly conserved catalytic domain acts on thousands of protein targets to
orchestrate myriad central biological roles. A major structural reorganization
of human calcineurin, a ubiquitous Ser/Thr PPP regulated by calcium and
calmodulin and targeted by immunosuppressant drugs cyclosporin A and FK506, is
unveiled here. The new conformation involves trans- to cis-isomerization of
proline in the SAPNY sequence, highly conserved across PPPs, and remodels the
main regulatory site where NFATc transcription factors bind. Transitions between
cis- and trans-conformations may involve peptidyl prolyl isomerases such as
cyclophilin A and FKBP12, which are known to physically interact with and
modulate calcineurin even in the absence of immunosuppressant drugs. Alternative
conformations in PPPs provide a new perspective on interactions with substrates
and other protein partners and may foster development of more specific
inhibitors as drug candidates.
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Links
