1TCO
TERNARY COMPLEX OF A CALCINEURIN A FRAGMENT, CALCINEURIN B, FKBP12 AND THE IMMUNOSUPPRESSANT DRUG FK506 (TACROLIMUS)
Functional Information from GO Data
| Chain | GOid | namespace | contents |
| A | 0016787 | molecular_function | hydrolase activity |
| A | 0033192 | molecular_function | calmodulin-dependent protein phosphatase activity |
| A | 0097720 | biological_process | calcineurin-mediated signaling |
| B | 0005509 | molecular_function | calcium ion binding |
| B | 0005829 | cellular_component | cytosol |
| B | 0005886 | cellular_component | plasma membrane |
| B | 0005955 | cellular_component | calcineurin complex |
| B | 0008597 | molecular_function | calcium-dependent protein serine/threonine phosphatase regulator activity |
| B | 0019902 | molecular_function | phosphatase binding |
| B | 0033173 | biological_process | calcineurin-NFAT signaling cascade |
| B | 0042383 | cellular_component | sarcolemma |
| B | 0046872 | molecular_function | metal ion binding |
| C | 0000413 | biological_process | protein peptidyl-prolyl isomerization |
| C | 0001933 | biological_process | negative regulation of protein phosphorylation |
| C | 0003007 | biological_process | heart morphogenesis |
| C | 0003755 | molecular_function | peptidyl-prolyl cis-trans isomerase activity |
| C | 0005528 | molecular_function | FK506 binding |
| C | 0005737 | cellular_component | cytoplasm |
| C | 0005829 | cellular_component | cytosol |
| C | 0006457 | biological_process | protein folding |
| C | 0006936 | biological_process | muscle contraction |
| C | 0007183 | biological_process | obsolete SMAD protein complex assembly |
| C | 0010881 | biological_process | regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion |
| C | 0016020 | cellular_component | membrane |
| C | 0016529 | cellular_component | sarcoplasmic reticulum |
| C | 0016853 | molecular_function | isomerase activity |
| C | 0019221 | biological_process | cytokine-mediated signaling pathway |
| C | 0019855 | molecular_function | calcium channel inhibitor activity |
| C | 0030018 | cellular_component | Z disc |
| C | 0031000 | biological_process | response to caffeine |
| C | 0031398 | biological_process | positive regulation of protein ubiquitination |
| C | 0032092 | biological_process | positive regulation of protein binding |
| C | 0032515 | biological_process | obsolete negative regulation of phosphoprotein phosphatase activity |
| C | 0032880 | biological_process | regulation of protein localization |
| C | 0032925 | biological_process | regulation of activin receptor signaling pathway |
| C | 0033017 | cellular_component | sarcoplasmic reticulum membrane |
| C | 0042098 | biological_process | T cell proliferation |
| C | 0042110 | biological_process | T cell activation |
| C | 0042803 | molecular_function | protein homodimerization activity |
| C | 0043123 | biological_process | positive regulation of canonical NF-kappaB signal transduction |
| C | 0044325 | molecular_function | transmembrane transporter binding |
| C | 0046332 | molecular_function | SMAD binding |
| C | 0048185 | molecular_function | activin binding |
| C | 0050776 | biological_process | regulation of immune response |
| C | 0051209 | biological_process | release of sequestered calcium ion into cytosol |
| C | 0051280 | biological_process | negative regulation of release of sequestered calcium ion into cytosol |
| C | 0055010 | biological_process | ventricular cardiac muscle tissue morphogenesis |
| C | 0060314 | biological_process | regulation of ryanodine-sensitive calcium-release channel activity |
| C | 0060315 | biological_process | negative regulation of ryanodine-sensitive calcium-release channel activity |
| C | 0060347 | biological_process | heart trabecula formation |
| C | 0070062 | cellular_component | extracellular exosome |
| C | 0097435 | biological_process | supramolecular fiber organization |
| C | 0098562 | cellular_component | cytoplasmic side of membrane |
| C | 1902991 | biological_process | regulation of amyloid precursor protein catabolic process |
| C | 1990000 | biological_process | amyloid fibril formation |
| C | 1990425 | cellular_component | ryanodine receptor complex |
Functional Information from PDB Data
| site_id | 506 |
| Number of Residues | 18 |
| Details | THE FK506 BINDING SITE ON FKBP12 (SUBUNIT C) AS WELL AS FK506 CONTACTS MADE TO CALCINEURIN-A (SUBUNIT A) AND CALCINEURIN-B (SUBUNIT B). |
| Chain | Residue |
| A | TRP352 |
| C | PHE46 |
| C | GLU54 |
| C | VAL55 |
| C | ILE56 |
| C | TRP59 |
| C | HIS87 |
| C | ILE91 |
| C | TYR82 |
| C | PHE99 |
| A | SER353 |
| A | PHE356 |
| B | LEU115 |
| B | MET118 |
| B | VAL119 |
| C | TYR26 |
| C | PHE36 |
| C | ASP37 |
| site_id | AC1 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE CA B 501 |
| Chain | Residue |
| B | ASP30 |
| B | ASP32 |
| B | SER34 |
| B | SER36 |
| B | GLU41 |
| site_id | AC2 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE CA B 502 |
| Chain | Residue |
| B | ASP62 |
| B | ASP64 |
| B | ASN66 |
| B | GLU68 |
| B | GLU73 |
| site_id | AC3 |
| Number of Residues | 6 |
| Details | BINDING SITE FOR RESIDUE CA B 503 |
| Chain | Residue |
| B | ASP99 |
| B | ASP101 |
| B | ASP103 |
| B | TYR105 |
| B | GLU110 |
| B | HOH619 |
| site_id | AC4 |
| Number of Residues | 6 |
| Details | BINDING SITE FOR RESIDUE CA B 504 |
| Chain | Residue |
| B | ASP140 |
| B | ASP142 |
| B | ASP144 |
| B | ARG146 |
| B | GLU151 |
| B | HOH636 |
| site_id | AC5 |
| Number of Residues | 7 |
| Details | BINDING SITE FOR RESIDUE ZN A 505 |
| Chain | Residue |
| A | ASP90 |
| A | ASP118 |
| A | ASN150 |
| A | HIS199 |
| A | HIS281 |
| A | FE506 |
| A | PO4507 |
| site_id | AC6 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE FE A 506 |
| Chain | Residue |
| A | ASP90 |
| A | HIS92 |
| A | ASP118 |
| A | ZN505 |
| A | PO4507 |
| site_id | AC7 |
| Number of Residues | 12 |
| Details | BINDING SITE FOR RESIDUE PO4 A 507 |
| Chain | Residue |
| A | HIS92 |
| A | ASP118 |
| A | ARG122 |
| A | ASN150 |
| A | HIS151 |
| A | ARG254 |
| A | HIS281 |
| A | TYR311 |
| A | ZN505 |
| A | FE506 |
| A | HOH524 |
| A | HOH663 |
| site_id | AC8 |
| Number of Residues | 11 |
| Details | BINDING SITE FOR RESIDUE MYR B 508 |
| Chain | Residue |
| A | LYS323 |
| A | GLU325 |
| A | ASN326 |
| A | VAL328 |
| A | ASN330 |
| B | GLY1 |
| B | ALA16 |
| B | ILE19 |
| B | LYS20 |
| B | GLY35 |
| B | PHE71 |
| site_id | AC9 |
| Number of Residues | 19 |
| Details | BINDING SITE FOR RESIDUE FK5 C 509 |
| Chain | Residue |
| A | TRP352 |
| A | SER353 |
| A | PHE356 |
| B | HOH516 |
| C | TYR26 |
| C | PHE36 |
| C | ASP37 |
| C | ARG42 |
| C | PHE46 |
| C | VAL55 |
| C | ILE56 |
| C | TRP59 |
| C | ALA81 |
| C | TYR82 |
| C | HIS87 |
| C | ILE91 |
| C | PHE99 |
| C | HOH511 |
| C | HOH520 |
Functional Information from PROSITE/UniProt
| site_id | PS00018 |
| Number of Residues | 13 |
| Details | EF_HAND_1 EF-hand calcium-binding domain. DLDNSGSLSveEF |
| Chain | Residue | Details |
| B | ASP30-PHE42 | |
| B | ASP62-PHE74 | |
| B | ASP99-LEU111 | |
| B | ASP140-PHE152 |
| site_id | PS00125 |
| Number of Residues | 6 |
| Details | SER_THR_PHOSPHATASE Serine/threonine specific protein phosphatases signature. LRGNHE |
| Chain | Residue | Details |
| A | LEU147-GLU152 |
Functional Information from SwissProt/UniProt
| site_id | SWS_FT_FI1 |
| Number of Residues | 284 |
| Details | Region: {"description":"Catalytic","evidences":[{"evidenceCode":"ECO:0000305"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI2 |
| Number of Residues | 9 |
| Details | Region: {"description":"Interaction with PxIxIF motif in substrate","evidences":[{"source":"UniProtKB","id":"Q08209","evidenceCode":"ECO:0000250"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI3 |
| Number of Residues | 28 |
| Details | Region: {"description":"Calcineurin B binding","evidences":[{"source":"PubMed","id":"16411749","evidenceCode":"ECO:0000269"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI4 |
| Number of Residues | 4 |
| Details | Motif: {"description":"SAPNY motif","evidences":[{"source":"UniProtKB","id":"Q08209","evidenceCode":"ECO:0000250"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI5 |
| Number of Residues | 1 |
| Details | Active site: {"description":"Proton donor","evidences":[{"source":"UniProtKB","id":"Q08209","evidenceCode":"ECO:0000250"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI6 |
| Number of Residues | 6 |
| Details | Binding site: {"evidences":[{"source":"PubMed","id":"7543369","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"1TCO","evidenceCode":"ECO:0007744"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI7 |
| Number of Residues | 1 |
| Details | Site: {"description":"Interaction with PxVP motif in substrate","evidences":[{"source":"UniProtKB","id":"Q08209","evidenceCode":"ECO:0000250"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI8 |
| Number of Residues | 1 |
| Details | Modified residue: {"description":"3'-nitrotyrosine","evidences":[{"source":"UniProtKB","id":"P63328","evidenceCode":"ECO:0000250"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI9 |
| Number of Residues | 28 |
| Details | Domain: {"description":"EF-hand 1","evidences":[{"source":"PROSITE-ProRule","id":"PRU00448","evidenceCode":"ECO:0000255"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI10 |
| Number of Residues | 35 |
| Details | Domain: {"description":"EF-hand 2","evidences":[{"source":"PROSITE-ProRule","id":"PRU00448","evidenceCode":"ECO:0000255"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI11 |
| Number of Residues | 35 |
| Details | Domain: {"description":"EF-hand 3","evidences":[{"source":"PROSITE-ProRule","id":"PRU00448","evidenceCode":"ECO:0000255"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI12 |
| Number of Residues | 35 |
| Details | Domain: {"description":"EF-hand 4","evidences":[{"source":"PROSITE-ProRule","id":"PRU00448","evidenceCode":"ECO:0000255"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI13 |
| Number of Residues | 5 |
| Details | Region: {"description":"Calcineurin A binding","evidences":[{"source":"PubMed","id":"7543369","evidenceCode":"ECO:0000269"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI14 |
| Number of Residues | 20 |
| Details | Binding site: {"evidences":[{"source":"PROSITE-ProRule","id":"PRU00448","evidenceCode":"ECO:0000255"},{"source":"PubMed","id":"7543369","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"1TCO","evidenceCode":"ECO:0007744"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI15 |
| Number of Residues | 2 |
| Details | Site: {"description":"Interaction with PxVP motif in substrates of the catalytic subunit","evidences":[{"source":"UniProtKB","id":"P63098","evidenceCode":"ECO:0000250"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI16 |
| Number of Residues | 1 |
| Details | Modified residue: {"description":"Phosphotyrosine","evidences":[{"source":"UniProtKB","id":"Q63810","evidenceCode":"ECO:0000250"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI17 |
| Number of Residues | 1 |
| Details | Lipidation: {"description":"N-myristoyl glycine","evidences":[{"source":"PubMed","id":"6321184","evidenceCode":"ECO:0000269"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI18 |
| Number of Residues | 88 |
| Details | Domain: {"description":"PPIase FKBP-type","evidences":[{"source":"PROSITE-ProRule","id":"PRU00277","evidenceCode":"ECO:0000255"}]} |
| Chain | Residue | Details |
| site_id | SWS_FT_FI19 |
| Number of Residues | 1 |
| Details | Modified residue: {"description":"N6-succinyllysine; alternate","evidences":[{"source":"UniProtKB","id":"P26883","evidenceCode":"ECO:0000250"}]} |
| Chain | Residue | Details |
Catalytic Information from CSA
| site_id | CSA1 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1aui |
| Chain | Residue | Details |
| A | ASP121 | |
| A | HIS151 |
| site_id | CSA2 |
| Number of Residues | 3 |
| Details | Annotated By Reference To The Literature 1aui |
| Chain | Residue | Details |
| C | ILE56 | |
| C | TYR82 | |
| C | ASP37 |
| site_id | MCSA1 |
| Number of Residues | 6 |
| Details | M-CSA 362 |
| Chain | Residue | Details |
| C | TYR26 | electrostatic destabiliser, steric role |
| C | PHE36 | electrostatic destabiliser, polar/non-polar interaction, steric role |
| C | ASP37 | electrostatic stabiliser, steric role |
| C | ILE56 | electrostatic stabiliser, steric role |
| C | TYR82 | electrostatic stabiliser, steric role |
| C | PHE99 | electrostatic destabiliser, polar/non-polar interaction, steric role |
