6lh4

From Proteopedia

(Difference between revisions)

Current revision

Crystal structural of MacroD1-ADPr complex

Structural highlights

6lh4 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.999Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MACD1_HUMAN A chromosomal aberration involving MACROD1 is found in acute leukemia. Translocation t(11;21)(q13;q22) that forms a RUNX1-MACROD1 fusion protein.

Function

MACD1_HUMAN Removes ADP-ribose from glutamate residues in proteins bearing a single ADP-ribose moiety. Inactive towards proteins bearing poly-ADP-ribose. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Plays a role in estrogen signaling. Binds to androgen receptor (AR) and amplifies the transactivation function of AR in response to androgen. May play an important role in carcinogenesis and/or progression of hormone-dependent cancers by feed-forward mechanism that activates ESR1 transactivation. Could be an ESR1 coactivator, providing a positive feedback regulatory loop for ESR1 signal transduction. Could be involved in invasive growth by down-regulating CDH1 in endometrial cancer cells. Enhances ESR1-mediated transcription activity.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

MacroD1 is an enzyme that hydrolyzes protein mono-ADP-ribosylation. However, the key catalytic residues of MacroD1 in these biochemical reactions remain elusive. Here, we present the crystal structure of MacroD1 in a complex with ADP-ribose (ADPR). The beta5-alpha10-loop functions as a switch loop to mediate substrate recognition and right orientation. The conserved Phe(272) in the beta5-alpha10-loop plays a crucial role in the orientation of ADPR distal ribose, and a conserved hydrogen-bond network contributes significantly to hold and orient the catalytic water12, which mediates ADPR hydrolysis. Moreover, we found that MacroD1 was recruited to the sites of DNA damage via recognition of ADP-ribosylation at DNA lesions. The MacroD1-mediated ADPR hydrolysis is essential for DNA damage repair. Taken together, our study provides structural and functional insights into the molecular mechanism of MacroD1-mediated ADPR hydrolysis and its role in DNA damage repair.

Molecular basis for the MacroD1-mediated hydrolysis of ADP-ribosylation.,Yang X, Ma Y, Li Y, Dong Y, Yu LL, Wang H, Guo L, Wu C, Yu X, Liu X DNA Repair (Amst). 2020 Oct;94:102899. doi: 10.1016/j.dnarep.2020.102899. Epub, 2020 Jun 22. PMID:32683309^[7]

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

References

↑ Meng YG, Han WD, Zhao YL, Huang K, Si YL, Wu ZQ, Mu YM. Induction of the LRP16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the downregulation of E-cadherin. Cell Res. 2007 Oct;17(10):869-80. PMID:17893710 doi:http://dx.doi.org/10.1038/cr.2007.79
↑ Han WD, Zhao YL, Meng YG, Zang L, Wu ZQ, Li Q, Si YL, Huang K, Ba JM, Morinaga H, Nomura M, Mu YM. Estrogenically regulated LRP16 interacts with estrogen receptor alpha and enhances the receptor's transcriptional activity. Endocr Relat Cancer. 2007 Sep;14(3):741-53. PMID:17914104 doi:http://dx.doi.org/10.1677/ERC-06-0082
↑ Yang J, Zhao YL, Wu ZQ, Si YL, Meng YG, Fu XB, Mu YM, Han WD. The single-macro domain protein LRP16 is an essential cofactor of androgen receptor. Endocr Relat Cancer. 2009 Mar;16(1):139-53. doi: 10.1677/ERC-08-0150. Epub 2008, Nov 20. PMID:19022849 doi:http://dx.doi.org/10.1677/ERC-08-0150
↑ Tian L, Wu Z, Zhao Y, Meng Y, Si Y, Fu X, Mu Y, Han W. Differential induction of LRP16 by liganded and unliganded estrogen receptor alpha in SKOV3 ovarian carcinoma cells. J Endocrinol. 2009 Jul;202(1):167-77. doi: 10.1677/JOE-09-0054. Epub 2009 Apr 29. PMID:19403568 doi:http://dx.doi.org/10.1677/JOE-09-0054
↑ Jankevicius G, Hassler M, Golia B, Rybin V, Zacharias M, Timinszky G, Ladurner AG. A family of macrodomain proteins reverses cellular mono-ADP-ribosylation. Nat Struct Mol Biol. 2013 Apr;20(4):508-14. doi: 10.1038/nsmb.2523. Epub 2013 Mar, 10. PMID:23474712 doi:http://dx.doi.org/10.1038/nsmb.2523
↑ Chen D, Vollmar M, Rossi MN, Phillips C, Kraehenbuehl R, Slade D, Mehrotra PV, von Delft F, Crosthwaite SK, Gileadi O, Denu JM, Ahel I. Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases. J Biol Chem. 2011 Apr 15;286(15):13261-71. Epub 2011 Jan 21. PMID:21257746 doi:10.1074/jbc.M110.206771
↑ Yang X, Ma Y, Li Y, Dong Y, Yu LL, Wang H, Guo L, Wu C, Yu X, Liu X. Molecular basis for the MacroD1-mediated hydrolysis of ADP-ribosylation. DNA Repair (Amst). 2020 Oct;94:102899. doi: 10.1016/j.dnarep.2020.102899. Epub, 2020 Jun 22. PMID:32683309 doi:http://dx.doi.org/10.1016/j.dnarep.2020.102899

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6lh4"

Categories: Homo sapiens | Large Structures | Li Y | Ma Y | Yang X

@@ Line 3: / Line 3: @@
 <StructureSection load='6lh4' size='340' side='right'caption='[[6lh4]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6lh4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LH4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6lh4]] is a 4 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=6LH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LH4 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</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]] 1.999&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MACROD1, LRP16 ([https://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=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</scene></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=6lh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lh4 OCA], [https://pdbe.org/6lh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lh4 RCSB], [https://www.ebi.ac.uk/pdbsum/6lh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lh4 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/MACD1_HUMAN MACD1_HUMAN]] A chromosomal aberration involving MACROD1 is found in acute leukemia. Translocation t(11;21)(q13;q22) that forms a RUNX1-MACROD1 fusion protein.
+[https://www.uniprot.org/uniprot/MACD1_HUMAN MACD1_HUMAN] A chromosomal aberration involving MACROD1 is found in acute leukemia. Translocation t(11;21)(q13;q22) that forms a RUNX1-MACROD1 fusion protein.
 == Function ==
-[[https://www.uniprot.org/uniprot/MACD1_HUMAN MACD1_HUMAN]] Removes ADP-ribose from glutamate residues in proteins bearing a single ADP-ribose moiety. Inactive towards proteins bearing poly-ADP-ribose. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Plays a role in estrogen signaling. Binds to androgen receptor (AR) and amplifies the transactivation function of AR in response to androgen. May play an important role in carcinogenesis and/or progression of hormone-dependent cancers by feed-forward mechanism that activates ESR1 transactivation. Could be an ESR1 coactivator, providing a positive feedback regulatory loop for ESR1 signal transduction. Could be involved in invasive growth by down-regulating CDH1 in endometrial cancer cells. Enhances ESR1-mediated transcription activity.<ref>PMID:17893710</ref> <ref>PMID:17914104</ref> <ref>PMID:19022849</ref> <ref>PMID:19403568</ref> <ref>PMID:23474712</ref> <ref>PMID:21257746</ref>
+[https://www.uniprot.org/uniprot/MACD1_HUMAN MACD1_HUMAN] Removes ADP-ribose from glutamate residues in proteins bearing a single ADP-ribose moiety. Inactive towards proteins bearing poly-ADP-ribose. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Plays a role in estrogen signaling. Binds to androgen receptor (AR) and amplifies the transactivation function of AR in response to androgen. May play an important role in carcinogenesis and/or progression of hormone-dependent cancers by feed-forward mechanism that activates ESR1 transactivation. Could be an ESR1 coactivator, providing a positive feedback regulatory loop for ESR1 signal transduction. Could be involved in invasive growth by down-regulating CDH1 in endometrial cancer cells. Enhances ESR1-mediated transcription activity.<ref>PMID:17893710</ref> <ref>PMID:17914104</ref> <ref>PMID:19022849</ref> <ref>PMID:19403568</ref> <ref>PMID:23474712</ref> <ref>PMID:21257746</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Li, Y]]
+[[Category: Li Y]]
-[[Category: Ma, Y]]
+[[Category: Ma Y]]
-[[Category: Yang, X]]
+[[Category: Yang X]]
-[[Category: Adpr]]
-[[Category: Catalysis]]
-[[Category: Dna repair]]
-[[Category: Hydrolase]]
-[[Category: Macrod1]]

6lh4

From Proteopedia

Current revision

Crystal structural of MacroD1-ADPr complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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