The mechanism of the elongation and branching reaction of Poly(ADP-ribose) polymerase as derived from crystal structures and mutagenesis
The binding site for the acceptor substrate poly(ADP-ribose) in the elongation reaction of the ADP-ribosyl transferase poly(ADP-ribose) polymerase (PARP) was detected by cocrystallizing the enzyme with an NAD + analogue. The site was confirmed by mutagenesis studies. In conjunction with the binding...
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| Veröffentlicht in: | J Mol Biol 1998-04, Vol.278 (1), p.57-65 |
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| creator | Ruf, Armin Rolli, Véronique de Murcia, Gilbert Schulz, Georg E |
| description | The binding site for the acceptor substrate poly(ADP-ribose) in the elongation reaction of the ADP-ribosyl transferase poly(ADP-ribose) polymerase (PARP) was detected by cocrystallizing the enzyme with an NAD
+ analogue. The site was confirmed by mutagenesis studies. In conjunction with the binding site of the donor NAD
+, the bound acceptor reveals the geometry of the elongation reaction. It shows in particular that the strictly conserved glutamate residue of all ADP-ribosylating enzymes (Glu988 of PARP) facilitates the reaction by polarizing both, donor and acceptor. Moreover, the binding properties of the acceptor site suggest a mechanism for the branching reaction, that also explains the dual specificity of this transferase for elongation and branching, which is unique among polymer-forming enzymes. |
| doi_str_mv | 10.1006/jmbi.1998.1673 |
| format | Article |
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+ analogue. The site was confirmed by mutagenesis studies. In conjunction with the binding site of the donor NAD
+, the bound acceptor reveals the geometry of the elongation reaction. It shows in particular that the strictly conserved glutamate residue of all ADP-ribosylating enzymes (Glu988 of PARP) facilitates the reaction by polarizing both, donor and acceptor. Moreover, the binding properties of the acceptor site suggest a mechanism for the branching reaction, that also explains the dual specificity of this transferase for elongation and branching, which is unique among polymer-forming enzymes.</description><identifier>ISSN: 0022-2836</identifier><identifier>EISSN: 1089-8638</identifier><identifier>DOI: 10.1006/jmbi.1998.1673</identifier><identifier>PMID: 9571033</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adenosine Diphosphate Ribose ; Adenosine Diphosphate Ribose - metabolism ; ADP-ribose acceptor ; ADP-ribosylation ; Animals ; Binding Sites ; Biochemistry, Molecular Biology ; Chickens ; Crystallography, X-Ray ; DNA-repair ; Enzyme Inhibitors ; Humans ; Life Sciences ; Models, Molecular ; Mutagenesis ; NAD ; NAD - analogs & derivatives ; NAD - chemistry ; NAD - metabolism ; Niacinamide ; Niacinamide - analogs & derivatives ; Peptide Fragments ; Peptide Fragments - chemistry ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases ; Poly(ADP-ribose) Polymerases - chemistry ; Poly(ADP-ribose) Polymerases - genetics ; Poly(ADP-ribose) Polymerases - metabolism ; polymer branching ; Structural Biology ; Structure-Activity Relationship ; X-ray structure analysis</subject><ispartof>J Mol Biol, 1998-04, Vol.278 (1), p.57-65</ispartof><rights>1998 Academic Press</rights><rights>Copyright 1998 Academic Press Limited.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-505f7806a8a467d9ba401e33cbc773061ff775a8ed7268117dd98635e4f1b0c53</citedby><cites>FETCH-LOGICAL-c470t-505f7806a8a467d9ba401e33cbc773061ff775a8ed7268117dd98635e4f1b0c53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/jmbi.1998.1673$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,882,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9571033$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02371500$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Ruf, Armin</creatorcontrib><creatorcontrib>Rolli, Véronique</creatorcontrib><creatorcontrib>de Murcia, Gilbert</creatorcontrib><creatorcontrib>Schulz, Georg E</creatorcontrib><title>The mechanism of the elongation and branching reaction of Poly(ADP-ribose) polymerase as derived from crystal structures and mutagenesis</title><title>J Mol Biol</title><addtitle>J Mol Biol</addtitle><description>The binding site for the acceptor substrate poly(ADP-ribose) in the elongation reaction of the ADP-ribosyl transferase poly(ADP-ribose) polymerase (PARP) was detected by cocrystallizing the enzyme with an NAD
+ analogue. The site was confirmed by mutagenesis studies. In conjunction with the binding site of the donor NAD
+, the bound acceptor reveals the geometry of the elongation reaction. It shows in particular that the strictly conserved glutamate residue of all ADP-ribosylating enzymes (Glu988 of PARP) facilitates the reaction by polarizing both, donor and acceptor. Moreover, the binding properties of the acceptor site suggest a mechanism for the branching reaction, that also explains the dual specificity of this transferase for elongation and branching, which is unique among polymer-forming enzymes.</description><subject>Adenosine Diphosphate Ribose</subject><subject>Adenosine Diphosphate Ribose - metabolism</subject><subject>ADP-ribose acceptor</subject><subject>ADP-ribosylation</subject><subject>Animals</subject><subject>Binding Sites</subject><subject>Biochemistry, Molecular Biology</subject><subject>Chickens</subject><subject>Crystallography, X-Ray</subject><subject>DNA-repair</subject><subject>Enzyme Inhibitors</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Models, Molecular</subject><subject>Mutagenesis</subject><subject>NAD</subject><subject>NAD - analogs & derivatives</subject><subject>NAD - chemistry</subject><subject>NAD - metabolism</subject><subject>Niacinamide</subject><subject>Niacinamide - analogs & derivatives</subject><subject>Peptide Fragments</subject><subject>Peptide Fragments - chemistry</subject><subject>Poly(ADP-ribose) Polymerase Inhibitors</subject><subject>Poly(ADP-ribose) Polymerases</subject><subject>Poly(ADP-ribose) Polymerases - chemistry</subject><subject>Poly(ADP-ribose) Polymerases - genetics</subject><subject>Poly(ADP-ribose) Polymerases - metabolism</subject><subject>polymer branching</subject><subject>Structural Biology</subject><subject>Structure-Activity Relationship</subject><subject>X-ray structure analysis</subject><issn>0022-2836</issn><issn>1089-8638</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFu1DAQhi0EKkvhyg3JJ0QPWcZxEjvHVQsUaSV6KGfLsSe7rhJ7sZOV9g14bJzuqjdOI_3zzX-Yj5CPDNYMoPn6NHZuzdpWrlkj-CuyYiDbQjZcviYrgLIsSsmbt-RdSk8AUPNKXpGrthYMOF-Rv497pCOavfYujTT0dMoBDsHv9OSCp9pb2kXtzd75HY2ozXOcwYcwnL5s7h6K6LqQ8IYecjBi1AmpTtRidEe0tI9hpCae0qQHmqY4m2mOmJ6Lx3nSO_SYXHpP3vR6SPjhMq_J7-_fHm_vi-2vHz9vN9vCVAKmooa6FxIaLXXVCNt2ugKGnJvOCMGhYX0vRK0lWlE2kjFhbZufUWPVsw5Mza_Jzbl3rwd1iG7U8aSCdup-s1VLBiUXrAY4ssx-PrOHGP7MmCY1umRwGLTHMCfFmkrKshUZXJ9BE0NKEfuXZgZq0aQWTWrRpBZN-eDTpXnuRrQv-MVL3svzHvMrjg6jSsahN2hdRDMpG9z_qv8BJGWiUw</recordid><startdate>19980424</startdate><enddate>19980424</enddate><creator>Ruf, Armin</creator><creator>Rolli, Véronique</creator><creator>de Murcia, Gilbert</creator><creator>Schulz, Georg E</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>1XC</scope></search><sort><creationdate>19980424</creationdate><title>The mechanism of the elongation and branching reaction of Poly(ADP-ribose) polymerase as derived from crystal structures and mutagenesis</title><author>Ruf, Armin ; Rolli, Véronique ; de Murcia, Gilbert ; Schulz, Georg E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-505f7806a8a467d9ba401e33cbc773061ff775a8ed7268117dd98635e4f1b0c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adenosine Diphosphate Ribose</topic><topic>Adenosine Diphosphate Ribose - metabolism</topic><topic>ADP-ribose acceptor</topic><topic>ADP-ribosylation</topic><topic>Animals</topic><topic>Binding Sites</topic><topic>Biochemistry, Molecular Biology</topic><topic>Chickens</topic><topic>Crystallography, X-Ray</topic><topic>DNA-repair</topic><topic>Enzyme Inhibitors</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Models, Molecular</topic><topic>Mutagenesis</topic><topic>NAD</topic><topic>NAD - analogs & derivatives</topic><topic>NAD - chemistry</topic><topic>NAD - metabolism</topic><topic>Niacinamide</topic><topic>Niacinamide - analogs & derivatives</topic><topic>Peptide Fragments</topic><topic>Peptide Fragments - chemistry</topic><topic>Poly(ADP-ribose) Polymerase Inhibitors</topic><topic>Poly(ADP-ribose) Polymerases</topic><topic>Poly(ADP-ribose) Polymerases - chemistry</topic><topic>Poly(ADP-ribose) Polymerases - genetics</topic><topic>Poly(ADP-ribose) Polymerases - metabolism</topic><topic>polymer branching</topic><topic>Structural Biology</topic><topic>Structure-Activity Relationship</topic><topic>X-ray structure analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ruf, Armin</creatorcontrib><creatorcontrib>Rolli, Véronique</creatorcontrib><creatorcontrib>de Murcia, Gilbert</creatorcontrib><creatorcontrib>Schulz, Georg E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>J Mol Biol</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ruf, Armin</au><au>Rolli, Véronique</au><au>de Murcia, Gilbert</au><au>Schulz, Georg E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The mechanism of the elongation and branching reaction of Poly(ADP-ribose) polymerase as derived from crystal structures and mutagenesis</atitle><jtitle>J Mol Biol</jtitle><addtitle>J Mol Biol</addtitle><date>1998-04-24</date><risdate>1998</risdate><volume>278</volume><issue>1</issue><spage>57</spage><epage>65</epage><pages>57-65</pages><issn>0022-2836</issn><eissn>1089-8638</eissn><abstract>The binding site for the acceptor substrate poly(ADP-ribose) in the elongation reaction of the ADP-ribosyl transferase poly(ADP-ribose) polymerase (PARP) was detected by cocrystallizing the enzyme with an NAD
+ analogue. The site was confirmed by mutagenesis studies. In conjunction with the binding site of the donor NAD
+, the bound acceptor reveals the geometry of the elongation reaction. It shows in particular that the strictly conserved glutamate residue of all ADP-ribosylating enzymes (Glu988 of PARP) facilitates the reaction by polarizing both, donor and acceptor. Moreover, the binding properties of the acceptor site suggest a mechanism for the branching reaction, that also explains the dual specificity of this transferase for elongation and branching, which is unique among polymer-forming enzymes.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>9571033</pmid><doi>10.1006/jmbi.1998.1673</doi><tpages>9</tpages></addata></record> |
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| ispartof | J Mol Biol, 1998-04, Vol.278 (1), p.57-65 |
| issn | 0022-2836 1089-8638 |
| language | eng |
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| subjects | Adenosine Diphosphate Ribose Adenosine Diphosphate Ribose - metabolism ADP-ribose acceptor ADP-ribosylation Animals Binding Sites Biochemistry, Molecular Biology Chickens Crystallography, X-Ray DNA-repair Enzyme Inhibitors Humans Life Sciences Models, Molecular Mutagenesis NAD NAD - analogs & derivatives NAD - chemistry NAD - metabolism Niacinamide Niacinamide - analogs & derivatives Peptide Fragments Peptide Fragments - chemistry Poly(ADP-ribose) Polymerase Inhibitors Poly(ADP-ribose) Polymerases Poly(ADP-ribose) Polymerases - chemistry Poly(ADP-ribose) Polymerases - genetics Poly(ADP-ribose) Polymerases - metabolism polymer branching Structural Biology Structure-Activity Relationship X-ray structure analysis |
| title | The mechanism of the elongation and branching reaction of Poly(ADP-ribose) polymerase as derived from crystal structures and mutagenesis |
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