6lur

From Proteopedia

(Difference between revisions)

Revision as of 14:54, 29 November 2023

Human PUF60 UHM domain (thioredoxin fusion) in complex with a small molecule binder

Structural highlights

6lur is a 8 chain structure with sequence from Escherichia coli K-12 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

THIO_ECOLI Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions.PUF60_HUMAN DNA- and RNA-binding protein, involved in several nuclear processes such as pre-mRNA splicing, apoptosis and transcription regulation. In association with FUBP1 regulates MYC transcription at the P2 promoter through the core-TFIIH basal transcription factor. Acts as a transcriptional repressor through the core-TFIIH basal transcription factor. Represses FUBP1-induced transcriptional activation but not basal transcription. Decreases ERCC3 helicase activity. Does not repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells. Is also involved in pre-mRNA splicing. Promotes splicing of an intron with weak 3'-splice site and pyrimidine tract in a cooperative manner with U2AF2. Involved in apoptosis induction when overexpressed in HeLa cells. Isoform 6 failed to repress MYC transcription and inhibited FIR-induced apoptosis in colorectal cancer. Isoform 6 may contribute to tumor progression by enabling increased MYC expression and greater resistance to apoptosis in tumors than in normal cells. Modulates alternative splicing of several mRNAs. Binds to relaxed DNA of active promoter regions. Binds to the pyrimidine tract and 3'-splice site regions of pre-mRNA; binding is enhanced in presence of U2AF2. Binds to Y5 RNA in association with TROVE2. Binds to poly(U) RNA.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Recently, there has been increasing interest in new modalities such as therapeutic antibodies and gene therapy at a number of pharmaceutical companies. Moreover, in small-molecule drug discovery at such companies, efforts have focused on hard-to-drug targets such as inhibiting protein-protein interactions. Biomolecular NMR spectroscopy has been used in drug discovery in a variety of ways, such as for the reliable detection of binding and providing three-dimensional structural information for structure-based drug design. The advantages of using NMR spectroscopy have been known for decades (Jahnke in J Biomol NMR 39:87-90, (2007); Gossert and Jahnke in Prog Nucl Magn Reson Spectrosc 97:82-125, (2016)). For tackling hard-to-drug targets and increasing the success in discovering drug molecules, in-depth analysis of drug-target protein interactions performed by biophysical methods will be more and more essential. Here, we review the advantages of NMR spectroscopy as a key technology of biophysical methods and also discuss issues such as using cutting-edge NMR spectrometers and increasing the demand of utilizing conformational dynamics information for promoting small-molecule drug discovery.

Revisiting biomolecular NMR spectroscopy for promoting small-molecule drug discovery.,Hanzawa H, Shimada T, Takahashi M, Takahashi H J Biomol NMR. 2020 Apr 18. pii: 10.1007/s10858-020-00314-0. doi:, 10.1007/s10858-020-00314-0. PMID:32306215^[7]

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

References

↑ Liu J, He L, Collins I, Ge H, Libutti D, Li J, Egly JM, Levens D. The FBP interacting repressor targets TFIIH to inhibit activated transcription. Mol Cell. 2000 Feb;5(2):331-41. PMID:10882074
↑ Page-McCaw PS, Amonlirdviman K, Sharp PA. PUF60: a novel U2AF65-related splicing activity. RNA. 1999 Dec;5(12):1548-60. PMID:10606266
↑ Liu J, Akoulitchev S, Weber A, Ge H, Chuikov S, Libutti D, Wang XW, Conaway JW, Harris CC, Conaway RC, Reinberg D, Levens D. Defective interplay of activators and repressors with TFIH in xeroderma pigmentosum. Cell. 2001 Feb 9;104(3):353-63. PMID:11239393
↑ Matsushita K, Tomonaga T, Shimada H, Shioya A, Higashi M, Matsubara H, Harigaya K, Nomura F, Libutti D, Levens D, Ochiai T. An essential role of alternative splicing of c-myc suppressor FUSE-binding protein-interacting repressor in carcinogenesis. Cancer Res. 2006 Feb 1;66(3):1409-17. PMID:16452196 doi:http://dx.doi.org/10.1158/0008-5472.CAN-04-4459
↑ Liu J, Kouzine F, Nie Z, Chung HJ, Elisha-Feil Z, Weber A, Zhao K, Levens D. The FUSE/FBP/FIR/TFIIH system is a molecular machine programming a pulse of c-myc expression. EMBO J. 2006 May 17;25(10):2119-30. Epub 2006 Apr 20. PMID:16628215 doi:http://dx.doi.org/7601101
↑ Hastings ML, Allemand E, Duelli DM, Myers MP, Krainer AR. Control of pre-mRNA splicing by the general splicing factors PUF60 and U2AF65. PLoS One. 2007 Jun 20;2(6):e538. PMID:17579712 doi:http://dx.doi.org/10.1371/journal.pone.0000538
↑ Hanzawa H, Shimada T, Takahashi M, Takahashi H. Revisiting biomolecular NMR spectroscopy for promoting small-molecule drug discovery. J Biomol NMR. 2020 Apr 18. pii: 10.1007/s10858-020-00314-0. doi:, 10.1007/s10858-020-00314-0. PMID:32306215 doi:http://dx.doi.org/10.1007/s10858-020-00314-0

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6lur"

Categories: Escherichia coli K-12 | Homo sapiens | Large Structures | Hanzawa H | Takahashi M

@@ Line 3: / Line 3: @@
 <StructureSection load='6lur' size='340' side='right'caption='[[6lur]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6lur]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LUR OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6LUR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6lur]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LUR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LUR FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EVU:4-[2-[4-(aminomethyl)phenyl]phenyl]piperazin-2-one'>EVU</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PUF60, FIR, ROBPI, SIAHBP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EVU:4-[2-[4-(aminomethyl)phenyl]phenyl]piperazin-2-one'>EVU</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6lur FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lur OCA], [http://pdbe.org/6lur PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lur RCSB], [http://www.ebi.ac.uk/pdbsum/6lur PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lur ProSAT]</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=6lur FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lur OCA], [https://pdbe.org/6lur PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lur RCSB], [https://www.ebi.ac.uk/pdbsum/6lur PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lur ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/THIO_ECOLI THIO_ECOLI]] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions.
+[https://www.uniprot.org/uniprot/THIO_ECOLI THIO_ECOLI] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions.[https://www.uniprot.org/uniprot/PUF60_HUMAN PUF60_HUMAN] DNA- and RNA-binding protein, involved in several nuclear processes such as pre-mRNA splicing, apoptosis and transcription regulation. In association with FUBP1 regulates MYC transcription at the P2 promoter through the core-TFIIH basal transcription factor. Acts as a transcriptional repressor through the core-TFIIH basal transcription factor. Represses FUBP1-induced transcriptional activation but not basal transcription. Decreases ERCC3 helicase activity. Does not repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells. Is also involved in pre-mRNA splicing. Promotes splicing of an intron with weak 3'-splice site and pyrimidine tract in a cooperative manner with U2AF2. Involved in apoptosis induction when overexpressed in HeLa cells. Isoform 6 failed to repress MYC transcription and inhibited FIR-induced apoptosis in colorectal cancer. Isoform 6 may contribute to tumor progression by enabling increased MYC expression and greater resistance to apoptosis in tumors than in normal cells. Modulates alternative splicing of several mRNAs. Binds to relaxed DNA of active promoter regions. Binds to the pyrimidine tract and 3'-splice site regions of pre-mRNA; binding is enhanced in presence of U2AF2. Binds to Y5 RNA in association with TROVE2. Binds to poly(U) RNA.<ref>PMID:10882074</ref> <ref>PMID:10606266</ref> <ref>PMID:11239393</ref> <ref>PMID:16452196</ref> <ref>PMID:16628215</ref> <ref>PMID:17579712</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Escherichia coli K-12]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Hanzawa, H]]
+[[Category: Hanzawa H]]
-[[Category: Takahashi, M]]
+[[Category: Takahashi M]]
-[[Category: Splicing]]
-[[Category: Splicing factor]]

6lur

From Proteopedia

Revision as of 14:54, 29 November 2023

Human PUF60 UHM domain (thioredoxin fusion) in complex with a small molecule binder

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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