6l8u
From Proteopedia
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<StructureSection load='6l8u' size='340' side='right'caption='[[6l8u]], [[Resolution|resolution]] 2.92Å' scene=''> | <StructureSection load='6l8u' size='340' side='right'caption='[[6l8u]], [[Resolution|resolution]] 2.92Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6l8u]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L8U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6L8U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6l8u]] is a 4 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=6L8U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6L8U FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCDIN3D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6l8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l8u OCA], [http://pdbe.org/6l8u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6l8u RCSB], [http://www.ebi.ac.uk/pdbsum/6l8u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6l8u ProSAT]</span></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=6l8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l8u OCA], [http://pdbe.org/6l8u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6l8u RCSB], [http://www.ebi.ac.uk/pdbsum/6l8u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6l8u ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/BN3D2_HUMAN BN3D2_HUMAN]] O-methyltransferase that specifically monomethylates 5'-monophosphate of cytoplasmic histidyl tRNA, acting as a capping enzyme (PubMed:28119416). Less efficiently, also methylates the 5' monophosphate of pre-miRNAs, acting as a negative regulator of miRNA processing (PubMed:23063121, PubMed:28119416). The 5' monophosphate of pre-miRNAs is recognized by DICER1 and is required for pre-miRNAs processing: methylation at this position reduces the processing of pre-miRNAs by DICER1. Able to mediate methylation of pre-miR-145, as well as other pre-miRNAs (PubMed:23063121). There is some controversy about the methylation of pre-miR-145, since the dimethylation first described as the specific enzymatic activity cannot be reproduced by a more recent work which observes a monomehtylation of pre-miR-145 but two orders weaker than the methylation of cytosolic histidyl tRNA (PubMed:23063121, PubMed:28119416, PubMed:30127802).<ref>PMID:23063121</ref> <ref>PMID:28119416</ref> <ref>PMID:30127802</ref> | [[http://www.uniprot.org/uniprot/BN3D2_HUMAN BN3D2_HUMAN]] O-methyltransferase that specifically monomethylates 5'-monophosphate of cytoplasmic histidyl tRNA, acting as a capping enzyme (PubMed:28119416). Less efficiently, also methylates the 5' monophosphate of pre-miRNAs, acting as a negative regulator of miRNA processing (PubMed:23063121, PubMed:28119416). The 5' monophosphate of pre-miRNAs is recognized by DICER1 and is required for pre-miRNAs processing: methylation at this position reduces the processing of pre-miRNAs by DICER1. Able to mediate methylation of pre-miR-145, as well as other pre-miRNAs (PubMed:23063121). There is some controversy about the methylation of pre-miR-145, since the dimethylation first described as the specific enzymatic activity cannot be reproduced by a more recent work which observes a monomehtylation of pre-miR-145 but two orders weaker than the methylation of cytosolic histidyl tRNA (PubMed:23063121, PubMed:28119416, PubMed:30127802).<ref>PMID:23063121</ref> <ref>PMID:28119416</ref> <ref>PMID:30127802</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | BCDIN3 domain containing RNA methyltransferase, BCDIN3D, monomethylates the 5'-monophosphate of cytoplasmic tRNAHis with a G-1:A73 mispair at the top of an eight-nucleotide-long acceptor helix, using S-adenosyl-l-methionine (SAM) as a methyl group donor. In humans, BCDIN3D overexpression is associated with the tumorigenic phenotype and poor prognosis in breast cancer. Here, we present the crystal structure of human BCDIN3D complexed with S-adenosyl-l-homocysteine. BCDIN3D adopts a classical Rossmann-fold methyltransferase structure. A comparison of the structure with that of the closely related methylphosphate capping enzyme, MePCE, which monomethylates the 5'-gamma-phosphate of 7SK RNA, revealed the important residues for monomethyl transfer from SAM onto the 5'-monophosphate of tRNAHis and for tRNAHis recognition by BCDIN3D. A structural model of tRNAHis docking onto BCDIN3D suggested the molecular mechanism underlying the different activities between BCDIN3D and MePCE. A loop in BCDIN3D is shorter, as compared to the corresponding region that forms an alpha-helix to recognize the 5'-end of RNA in MePCE, and the G-1:A73 mispair in tRNAHis allows the N-terminal alpha-helix of BCDIN3D to wedge the G-1:A73 mispair of tRNAHis. As a result, the 5'-monophosphate of G-1 of tRNAHis is deep in the catalytic pocket for 5'-phosphate methylation. Thus, BCDIN3D is a tRNAHis-specific 5'-monomethylphosphate capping enzyme that discriminates tRNAHis from other tRNA species, and the structural information presented in this study also provides the molecular basis for the development of drugs against breast cancers. | ||
| + | |||
| + | Crystal structure of human cytoplasmic tRNAHis-specific 5'-monomethylphosphate capping enzyme.,Liu Y, Martinez A, Yamashita S, Tomita K Nucleic Acids Res. 2020 Jan 10. pii: 5699672. doi: 10.1093/nar/gkz1216. PMID:31919512<ref>PMID:31919512</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6l8u" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Liu, Y]] | [[Category: Liu, Y]] | ||
Revision as of 16:38, 22 January 2020
Crystal structure of human BCDIN3D in complex with SAH
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