1cqg

From Proteopedia

(Difference between revisions)

Current revision

HIGH RESOLUTION SOLUTION NMR STRUCTURE OF MIXED DISULFIDE INTERMEDIATE BETWEEN HUMAN THIOREDOXIN (C35A, C62A, C69A, C73A) MUTANT AND A 13 RESIDUE PEPTIDE COMPRISING ITS TARGET SITE IN HUMAN REF-1 (RESIDUES 59-71 OF THE P50 SUBUNIT OF NFKB), NMR, 31 STRUCTURES

Structural highlights

1cqg is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 35 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

THIO_HUMAN Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity.^[1] ^[2] ^[3] ^[4] ^[5] ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55).^[6] ^[7] ^[8] ^[9] ^[10]

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

BACKGROUND: Human thioredoxin (hTRX) is a 12 kDa cellular redox protein that has been shown to play an important role in the activation of a number of transcriptional and translational regulators via a thiol-redox mechanism. This activity may be direct or indirect via another redox protein known as Ref-1. The structure of a complex of hTRX with a peptide comprising its target from the transcription factor NF kappa B has previously been solved. To further extend our knowledge of the recognition by and interaction of hTRX with its various targets, we have studied a complex between hTRX and a Ref-1 peptide. This complex represents a kinetically stable mixed disulfide intermediate along the reaction pathway. RESULTS: Using multidimensional heteronuclear edited and filtered NMR spectroscopy, we have solved the solution structure of a complex between hTRX and a 13-residue peptide comprising residues 59-71 of Ref-1. The Ref-1 peptide is located in a crescent-shaped groove on the surface of hTRX, the groove being formed by residues in the active-site loop (residues 32-36), helix 3, beta strands 3 and 5, and the loop between beta strands 3 and 4. The complex is stabilized by numerous hydrogen-bonding and hydrophobic interactions that involve residues 61-69 of the peptide and confer substrate specificity. CONCLUSIONS: The orientation of the Ref-1 peptide in the hTRX-Ref-1 complex is opposite to that found in the previously solved complex of hTRX with the target peptide from the transcription factor NF kappa B. Orientation is determined by three discriminating interactions involving the nature of the residues at the P-2' P-4 and P-5 binding positions. (P0 defines the active cysteine of the peptide, Cys65 for Ref-1 and Cys62 for NF kappa B. Positive and negative numbers indicate residues N-terminal and C-terminal to this residue, respectively, and vice versa for NF kappa B as it binds in the opposite orientation.) The environment surrounding the reactive Cys32 of hTRX, as well as the packing of the P+3 to P-4 residues are essentially the same in the two complexes, despite the opposing orientation of the peptide chains. This versatility in substrate recognition permits hTRX to act as a wide-ranging redox regulator for the cell.

The solution structure of human thioredoxin complexed with its target from Ref-1 reveals peptide chain reversal.,Qin J, Clore GM, Kennedy WP, Kuszewski J, Gronenborn AM Structure. 1996 May 15;4(5):613-20. PMID:8736558^[11]

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

References

↑ Jacquot JP, de Lamotte F, Fontecave M, Schurmann P, Decottignies P, Miginiac-Maslow M, Wollman E. Human thioredoxin reactivity-structure/function relationship. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1375-81. PMID:2176490
↑ Hirota K, Matsui M, Iwata S, Nishiyama A, Mori K, Yodoi J. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3633-8. PMID:9108029
↑ Wei SJ, Botero A, Hirota K, Bradbury CM, Markovina S, Laszlo A, Spitz DR, Goswami PC, Yodoi J, Gius D. Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation. Cancer Res. 2000 Dec 1;60(23):6688-95. PMID:11118054
↑ Mitchell DA, Marletta MA. Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine. Nat Chem Biol. 2005 Aug;1(3):154-8. Epub 2005 Jul 10. PMID:16408020 doi:http://dx.doi.org/nchembio720
↑ Mitchell DA, Morton SU, Fernhoff NB, Marletta MA. Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11609-14. Epub 2007 Jul 2. PMID:17606900 doi:http://dx.doi.org/0704898104
↑ Jacquot JP, de Lamotte F, Fontecave M, Schurmann P, Decottignies P, Miginiac-Maslow M, Wollman E. Human thioredoxin reactivity-structure/function relationship. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1375-81. PMID:2176490
↑ Hirota K, Matsui M, Iwata S, Nishiyama A, Mori K, Yodoi J. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3633-8. PMID:9108029
↑ Wei SJ, Botero A, Hirota K, Bradbury CM, Markovina S, Laszlo A, Spitz DR, Goswami PC, Yodoi J, Gius D. Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation. Cancer Res. 2000 Dec 1;60(23):6688-95. PMID:11118054
↑ Mitchell DA, Marletta MA. Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine. Nat Chem Biol. 2005 Aug;1(3):154-8. Epub 2005 Jul 10. PMID:16408020 doi:http://dx.doi.org/nchembio720
↑ Mitchell DA, Morton SU, Fernhoff NB, Marletta MA. Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11609-14. Epub 2007 Jul 2. PMID:17606900 doi:http://dx.doi.org/0704898104
↑ Qin J, Clore GM, Kennedy WP, Kuszewski J, Gronenborn AM. The solution structure of human thioredoxin complexed with its target from Ref-1 reveals peptide chain reversal. Structure. 1996 May 15;4(5):613-20. PMID:8736558

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1cqg"

Categories: Homo sapiens | Large Structures | Clore GM | Gronenborn AM | Qin J

@@ Line 1: / Line 1: @@
 ==HIGH RESOLUTION SOLUTION NMR STRUCTURE OF MIXED DISULFIDE INTERMEDIATE BETWEEN HUMAN THIOREDOXIN (C35A, C62A, C69A, C73A) MUTANT AND A 13 RESIDUE PEPTIDE COMPRISING ITS TARGET SITE IN HUMAN REF-1 (RESIDUES 59-71 OF THE P50 SUBUNIT OF NFKB), NMR, 31 STRUCTURES==
-<StructureSection load='1cqg' size='340' side='right'caption='[[1cqg]], [[NMR_Ensembles_of_Models | 35 NMR models]]' scene=''>
+<StructureSection load='1cqg' size='340' side='right'caption='[[1cqg]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1cqg]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CQG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CQG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1cqg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CQG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CQG FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1cqh|1cqh]]</div></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 35 models</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/DNA-(apurinic_or_apyrimidinic_site)_lyase DNA-(apurinic or apyrimidinic site) lyase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.99.18 4.2.99.18] </span></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=1cqg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cqg OCA], [https://pdbe.org/1cqg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cqg RCSB], [https://www.ebi.ac.uk/pdbsum/1cqg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cqg ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/THIO_HUMAN THIO_HUMAN]] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity.<ref>PMID:2176490</ref> <ref>PMID:9108029</ref> <ref>PMID:11118054</ref> <ref>PMID:16408020</ref> <ref>PMID:17606900</ref>   ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55).<ref>PMID:2176490</ref> <ref>PMID:9108029</ref> <ref>PMID:11118054</ref> <ref>PMID:16408020</ref> <ref>PMID:17606900</ref>  [[https://www.uniprot.org/uniprot/APEX1_HUMAN APEX1_HUMAN]] Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA.<ref>PMID:1719477</ref> <ref>PMID:12524539</ref> <ref>PMID:8355688</ref> <ref>PMID:8621488</ref> <ref>PMID:8932375</ref> <ref>PMID:9108029</ref> <ref>PMID:9207062</ref> <ref>PMID:9804799</ref> <ref>PMID:9560228</ref> <ref>PMID:10023679</ref> <ref>PMID:11118054</ref> <ref>PMID:11452037</ref> <ref>PMID:11832948</ref> <ref>PMID:11809897</ref> <ref>PMID:16617147</ref> <ref>PMID:18439621</ref> <ref>PMID:18809583</ref> <ref>PMID:18179823</ref> <ref>PMID:18579163</ref> <ref>PMID:19188445</ref> <ref>PMID:19401441</ref> <ref>PMID:19934257</ref> <ref>PMID:20699270</ref> <ref>PMID:21496894</ref> <ref>PMID:21762700</ref>
+[https://www.uniprot.org/uniprot/THIO_HUMAN THIO_HUMAN] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity.<ref>PMID:2176490</ref> <ref>PMID:9108029</ref> <ref>PMID:11118054</ref> <ref>PMID:16408020</ref> <ref>PMID:17606900</ref>   ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55).<ref>PMID:2176490</ref> <ref>PMID:9108029</ref> <ref>PMID:11118054</ref> <ref>PMID:16408020</ref> <ref>PMID:17606900</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
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   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cq/1cqg_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 36: / Line 35: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Clore, G M]]
+[[Category: Clore GM]]
-[[Category: Gronenborn, A M]]
+[[Category: Gronenborn AM]]
-[[Category: Qin, J]]
+[[Category: Qin J]]
-[[Category: Complex]]
-[[Category: Electron transport/peptide]]

1cqg

From Proteopedia

Current revision

HIGH RESOLUTION SOLUTION NMR STRUCTURE OF MIXED DISULFIDE INTERMEDIATE BETWEEN HUMAN THIOREDOXIN (C35A, C62A, C69A, C73A) MUTANT AND A 13 RESIDUE PEPTIDE COMPRISING ITS TARGET SITE IN HUMAN REF-1 (RESIDUES 59-71 OF THE P50 SUBUNIT OF NFKB), NMR, 31 STRUCTURES

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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