6b0q: Difference between revisions

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 ==Zinc finger Domain of WT1(-KTS form) with 13+1mer Oligonucleotide with 3' Triplet TGT==
-<StructureSection load='6b0q' size='340' side='right' caption='[[6b0q]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
+<StructureSection load='6b0q' size='340' side='right'caption='[[6b0q]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6b0q]] is a 6 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=6B0Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B0Q FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6b0q]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B0Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B0Q FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.794&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">WT1 ([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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6b0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b0q OCA], [http://pdbe.org/6b0q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b0q RCSB], [http://www.ebi.ac.uk/pdbsum/6b0q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b0q 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=6b0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b0q OCA], [https://pdbe.org/6b0q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b0q RCSB], [https://www.ebi.ac.uk/pdbsum/6b0q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b0q ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/WT1_HUMAN WT1_HUMAN]] Defects in WT1 are the cause of Frasier syndrome (FS) [MIM:[http://omim.org/entry/136680 136680]]. FS is characterized by a slowly progressing nephropathy leading to renal failure in adolescence or early adulthood, male pseudohermaphroditism, and no Wilms tumor. As for histological findings of the kidneys, focal glomerular sclerosis is often observed. There is phenotypic overlap with Denys-Drash syndrome. Inheritance is autosomal dominant.<ref>PMID:10571943</ref>   Defects in WT1 are the cause of Wilms tumor 1 (WT1) [MIM:[http://omim.org/entry/194070 194070]]. WT is an embryonal malignancy of the kidney that affects approximately 1 in 10'000 infants and young children. It occurs both in sporadic and hereditary forms.<ref>PMID:1317572</ref> <ref>PMID:9108089</ref> <ref>PMID:9529364</ref> <ref>PMID:15150775</ref>   Defects in WT1 are the cause of Denys-Drash syndrome (DDS) [MIM:[http://omim.org/entry/194080 194080]]. DDS is a typical nephropathy characterized by diffuse mesangial sclerosis, genital abnormalities, and/or Wilms tumor. There is phenotypic overlap with WAGR syndrome and Frasier syndrome. Inheritance is autosomal dominant, but most cases are sporadic.<ref>PMID:9529364</ref> <ref>PMID:1655284</ref> <ref>PMID:1302008</ref> <ref>PMID:1338906</ref> <ref>PMID:8388765</ref> <ref>PMID:8111391</ref> <ref>PMID:8295405</ref> <ref>PMID:8411073</ref> <ref>PMID:8112732</ref> <ref>PMID:8741319</ref> <ref>PMID:8956030</ref> <ref>PMID:9475094</ref> <ref>PMID:10738002</ref> <ref>PMID:11182928</ref> <ref>PMID:10799199</ref> <ref>PMID:11519891</ref> <ref>PMID:15349765</ref>   Defects in WT1 are the cause of nephrotic syndrome type 4 (NPHS4) [MIM:[http://omim.org/entry/256370 256370]]. A renal disease characterized clinically by proteinuria, hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. Most patients with NPHS4 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen.<ref>PMID:9529364</ref> <ref>PMID:11182928</ref> <ref>PMID:9607189</ref> <ref>PMID:15253707</ref>   Defects in WT1 are a cause of Meacham syndrome (MEACHS) [MIM:[http://omim.org/entry/608978 608978]]. Meacham syndrome is a rare sporadically occurring multiple malformation syndrome characterized by male pseudohermaphroditism with abnormal internal female genitalia comprising a uterus and double or septate vagina, complex congenital heart defect and diaphragmatic abnormalities.<ref>PMID:17853480</ref>   Note=A chromosomal aberration involving WT1 may be a cause of desmoplastic small round cell tumor (DSRCT). Translocation t(11;22)(p13;q12) with EWSR1.  Defects in WT1 may be a cause of mesothelioma malignant (MESOM) [MIM:[http://omim.org/entry/156240 156240]]. An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos.<ref>PMID:8401592</ref>
+[https://www.uniprot.org/uniprot/WT1_HUMAN WT1_HUMAN] Defects in WT1 are the cause of Frasier syndrome (FS) [MIM:[https://omim.org/entry/136680 136680]. FS is characterized by a slowly progressing nephropathy leading to renal failure in adolescence or early adulthood, male pseudohermaphroditism, and no Wilms tumor. As for histological findings of the kidneys, focal glomerular sclerosis is often observed. There is phenotypic overlap with Denys-Drash syndrome. Inheritance is autosomal dominant.<ref>PMID:10571943</ref>   Defects in WT1 are the cause of Wilms tumor 1 (WT1) [MIM:[https://omim.org/entry/194070 194070]. WT is an embryonal malignancy of the kidney that affects approximately 1 in 10'000 infants and young children. It occurs both in sporadic and hereditary forms.<ref>PMID:1317572</ref> <ref>PMID:9108089</ref> <ref>PMID:9529364</ref> <ref>PMID:15150775</ref>   Defects in WT1 are the cause of Denys-Drash syndrome (DDS) [MIM:[https://omim.org/entry/194080 194080]. DDS is a typical nephropathy characterized by diffuse mesangial sclerosis, genital abnormalities, and/or Wilms tumor. There is phenotypic overlap with WAGR syndrome and Frasier syndrome. Inheritance is autosomal dominant, but most cases are sporadic.<ref>PMID:9529364</ref> <ref>PMID:1655284</ref> <ref>PMID:1302008</ref> <ref>PMID:1338906</ref> <ref>PMID:8388765</ref> <ref>PMID:8111391</ref> <ref>PMID:8295405</ref> <ref>PMID:8411073</ref> <ref>PMID:8112732</ref> <ref>PMID:8741319</ref> <ref>PMID:8956030</ref> <ref>PMID:9475094</ref> <ref>PMID:10738002</ref> <ref>PMID:11182928</ref> <ref>PMID:10799199</ref> <ref>PMID:11519891</ref> <ref>PMID:15349765</ref>   Defects in WT1 are the cause of nephrotic syndrome type 4 (NPHS4) [MIM:[https://omim.org/entry/256370 256370]. A renal disease characterized clinically by proteinuria, hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. Most patients with NPHS4 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen.<ref>PMID:9529364</ref> <ref>PMID:11182928</ref> <ref>PMID:9607189</ref> <ref>PMID:15253707</ref>   Defects in WT1 are a cause of Meacham syndrome (MEACHS) [MIM:[https://omim.org/entry/608978 608978]. Meacham syndrome is a rare sporadically occurring multiple malformation syndrome characterized by male pseudohermaphroditism with abnormal internal female genitalia comprising a uterus and double or septate vagina, complex congenital heart defect and diaphragmatic abnormalities.<ref>PMID:17853480</ref>   Note=A chromosomal aberration involving WT1 may be a cause of desmoplastic small round cell tumor (DSRCT). Translocation t(11;22)(p13;q12) with EWSR1.  Defects in WT1 may be a cause of mesothelioma malignant (MESOM) [MIM:[https://omim.org/entry/156240 156240]. An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos.<ref>PMID:8401592</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/WT1_HUMAN WT1_HUMAN]] Transcription factor that plays an important role in cellular development and cell survival. Regulates the expression of numerous target genes, including EPO. Plays an essential role for development of the urogenital system. Recognizes and binds to the DNA sequence 5'-CGCCCCCGC-3'. It has a tumor suppressor as well as an oncogenic role in tumor formation. Function may be isoform-specific: isoforms lacking the KTS motif may act as transcription factors. Isoforms containing the KTS motif may bind mRNA and play a role in mRNA metabolism or splicing. Isoform 1 has lower affinity for DNA, and can bind RNA.<ref>PMID:19123921</ref> <ref>PMID:19416806</ref>
+[https://www.uniprot.org/uniprot/WT1_HUMAN WT1_HUMAN] Transcription factor that plays an important role in cellular development and cell survival. Regulates the expression of numerous target genes, including EPO. Plays an essential role for development of the urogenital system. Recognizes and binds to the DNA sequence 5'-CGCCCCCGC-3'. It has a tumor suppressor as well as an oncogenic role in tumor formation. Function may be isoform-specific: isoforms lacking the KTS motif may act as transcription factors. Isoforms containing the KTS motif may bind mRNA and play a role in mRNA metabolism or splicing. Isoform 1 has lower affinity for DNA, and can bind RNA.<ref>PMID:19123921</ref> <ref>PMID:19416806</ref>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Wilms tumor protein (WT1) is a Cys2-His2 zinc-finger transcription factor vital for embryonic development of the genitourinary system. The protein contains a C-terminal DNA binding domain with four tandem zinc-fingers (ZF1-4). An alternative splicing of Wt1 can add three additional amino acids-lysine (K), threonine (T) and serine (S)-between ZF3 and ZF4. In the -KTS isoform, ZF2-4 determine the sequence-specificity of DNA binding, whereas the function of ZF1 remains elusive. Three X-ray structures are described here for wild-type -KTS isoform ZF1-4 in complex with its cognate DNA sequence. We observed four unique ZF1 conformations. First, like ZF2-4, ZF1 can be positioned continuously in the DNA major groove forming a 'near-cognate' complex. Second, while ZF2-4 make base-specific interactions with one DNA molecule, ZF1 can interact with a second DNA molecule (or, presumably, two regions of the same DNA molecule). Third, ZF1 can intercalate at the joint of two tail-to-head DNA molecules. If such intercalation occurs on a continuous DNA molecule, it would kink the DNA at the ZF1 binding site. Fourth, two ZF1 units can dimerize. Furthermore, we examined a Denys-Drash syndrome-associated ZF1 mutation (methionine at position 342 is replaced by arginine). This mutation enhances WT1 affinity for a guanine base. X-ray crystallography of the mutant in complex with its preferred sequence revealed the interactions responsible for this affinity change. These results provide insight into the mechanisms of action of WT1, and clarify the fact that ZF1 plays a role in determining sequence specificity of this critical transcription factor.
-Role for first zinc finger of WT1 in DNA sequence specificity: Denys-Drash syndrome-associated WT1 mutant in ZF1 enhances affinity for a subset of WT1 binding sites.,Wang D, Horton JR, Zheng Y, Blumenthal RM, Zhang X, Cheng X Nucleic Acids Res. 2017 Dec 27. pii: 4780158. doi: 10.1093/nar/gkx1274. PMID:29294058<ref>PMID:29294058</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 6b0q" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Cheng, X]]
+[[Category: Large Structures]]
-[[Category: Horton, J R]]
+[[Category: Cheng X]]
-[[Category: Protein-dna complex wilms tumor suppressor protein zinc-finger]]
+[[Category: Horton JR]]
-[[Category: Transcription-dna complex]]