Phosphorus-containing inhibitors of aspartate transcarbamoylase from Escherichia coli
A tetrahedral intermediate is the prominent feature of the generally accepted mechanism for aspartate transcarbamoylase. We have synthesized N-pyrophosphoryl-L-aspartate as a charged analogue of the postulated intermediate. Surprisingly, its affinity for the enzyme from Escherichia coli was substant...
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| Veröffentlicht in: | FEBS letters 1990-01, Vol.260 (2), p.206-208 |
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| creator | Laing, Naomi Chan, William W.-C. Hutchinsoi, David W. Öberg, Bo |
| description | A tetrahedral intermediate is the prominent feature of the generally accepted mechanism for aspartate transcarbamoylase. We have synthesized
N-pyrophosphoryl-L-aspartate as a charged analogue of the postulated intermediate. Surprisingly, its affinity for the enzyme from
Escherichia coli was substantially lower than that of the previously known inhibitor phosphonoacetyl-L-aspartate which contained a trigonal carbonyl group. Similar results were obtained with the corresponding mercaptosuccinate derivatives. We also tested a number of new pyrophosphate analogues as inhibitors. Our results cast doubt on some aspects of the current model for the mechanism of this enzyme. |
| doi_str_mv | 10.1016/0014-5793(90)80104-Q |
| format | Article |
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N-pyrophosphoryl-L-aspartate as a charged analogue of the postulated intermediate. Surprisingly, its affinity for the enzyme from
Escherichia coli was substantially lower than that of the previously known inhibitor phosphonoacetyl-L-aspartate which contained a trigonal carbonyl group. Similar results were obtained with the corresponding mercaptosuccinate derivatives. We also tested a number of new pyrophosphate analogues as inhibitors. Our results cast doubt on some aspects of the current model for the mechanism of this enzyme.</description><identifier>ISSN: 0014-5793</identifier><identifier>EISSN: 1873-3468</identifier><identifier>DOI: 10.1016/0014-5793(90)80104-Q</identifier><identifier>PMID: 2153584</identifier><identifier>CODEN: FEBLAL</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Analytical, structural and metabolic biochemistry ; aspartate carbamoyltransferase ; Aspartate Carbamoyltransferase - antagonists & inhibitors ; Aspartate transcarbamoylase ; Aspartic Acid - analogs & derivatives ; Aspartic Acid - pharmacology ; ATCase ; Binding Sites - drug effects ; Biological and medical sciences ; Diphosphates - analysis ; Diphosphates - pharmacology ; Enzyme inhibition ; Enzymes and enzyme inhibitors ; Escherichia coli ; Escherichia coli - enzymology ; Fundamental and applied biological sciences. Psychology ; Magnetic Resonance Spectroscopy ; Molecular Structure ; n-phosphonoacetyl-L-aspartate ; N-Pyrophosphoryl-L-aspartate ; PALA ; Phosphonoacetic Acid - analogs & derivatives ; Phosphonoacetic Acid - pharmacology ; phosphonoacetyl-L-aspartate ; Structure-Activity Relationship ; Sulfhydryl Compounds - analysis ; Transferases ; Transition state</subject><ispartof>FEBS letters, 1990-01, Vol.260 (2), p.206-208</ispartof><rights>1990</rights><rights>FEBS Letters 260 (1990) 1873-3468 © 2015 Federation of European Biochemical Societies</rights><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c551Q-6d11d1f27193cc6888ba2177903b7834c37e34e18d93bca2755fdf7e54a858563</citedby><cites>FETCH-LOGICAL-c551Q-6d11d1f27193cc6888ba2177903b7834c37e34e18d93bca2755fdf7e54a858563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0014-5793(90)80104-Q$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19737356$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2153584$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Laing, Naomi</creatorcontrib><creatorcontrib>Chan, William W.-C.</creatorcontrib><creatorcontrib>Hutchinsoi, David W.</creatorcontrib><creatorcontrib>Öberg, Bo</creatorcontrib><title>Phosphorus-containing inhibitors of aspartate transcarbamoylase from Escherichia coli</title><title>FEBS letters</title><addtitle>FEBS Lett</addtitle><description>A tetrahedral intermediate is the prominent feature of the generally accepted mechanism for aspartate transcarbamoylase. We have synthesized
N-pyrophosphoryl-L-aspartate as a charged analogue of the postulated intermediate. Surprisingly, its affinity for the enzyme from
Escherichia coli was substantially lower than that of the previously known inhibitor phosphonoacetyl-L-aspartate which contained a trigonal carbonyl group. Similar results were obtained with the corresponding mercaptosuccinate derivatives. We also tested a number of new pyrophosphate analogues as inhibitors. Our results cast doubt on some aspects of the current model for the mechanism of this enzyme.</description><subject>Analytical, structural and metabolic biochemistry</subject><subject>aspartate carbamoyltransferase</subject><subject>Aspartate Carbamoyltransferase - antagonists & inhibitors</subject><subject>Aspartate transcarbamoylase</subject><subject>Aspartic Acid - analogs & derivatives</subject><subject>Aspartic Acid - pharmacology</subject><subject>ATCase</subject><subject>Binding Sites - drug effects</subject><subject>Biological and medical sciences</subject><subject>Diphosphates - analysis</subject><subject>Diphosphates - pharmacology</subject><subject>Enzyme inhibition</subject><subject>Enzymes and enzyme inhibitors</subject><subject>Escherichia coli</subject><subject>Escherichia coli - enzymology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Molecular Structure</subject><subject>n-phosphonoacetyl-L-aspartate</subject><subject>N-Pyrophosphoryl-L-aspartate</subject><subject>PALA</subject><subject>Phosphonoacetic Acid - analogs & derivatives</subject><subject>Phosphonoacetic Acid - pharmacology</subject><subject>phosphonoacetyl-L-aspartate</subject><subject>Structure-Activity Relationship</subject><subject>Sulfhydryl Compounds - analysis</subject><subject>Transferases</subject><subject>Transition state</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkEFv1DAQhS0EareFf9BKuYDaQ8CO49i-INFqF5AqwUr0bDnOpDFK4sWTpdp_X2d3VW7AyfK8N29mPkIuGH3PKKs-UMrKXEjNrzS9VpTRMl-_IAumJM95WamXZPFsOSVniD9p-iumT8hJwQQXqlyQ--9dwE0X4hZzF8bJ-tGPD5kfO1_7KUTMQptZ3Ng42QmyKdoRnY21HcKutwhZG8OQLdF1EL3rvM1c6P1r8qq1PcKb43tO7lfLH7df8rtvn7_efrrLnRBsnVcNYw1rC8k0d65SStW2YFJqymupeOm4BF4CU43mtbOFFKJtWgmitEooUfFz8u6Qu4nh1xZwMoNHB31vRwhbNFILLXVK_5eRCZGmC5mM5cHoYkCM0JpN9IONO8OombGbmamZmRpNzR67Wae2y2P-th6geW46ck7626NuE76-TRidxz_ZWnLJ9wetDr5H38Puv2ab1fKmmIW5rum-Oi_08RAECf9vD9Gg8zA6aHwEN5km-L9f9AQDgbJE</recordid><startdate>19900129</startdate><enddate>19900129</enddate><creator>Laing, Naomi</creator><creator>Chan, William W.-C.</creator><creator>Hutchinsoi, David W.</creator><creator>Öberg, Bo</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><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>7QL</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M81</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19900129</creationdate><title>Phosphorus-containing inhibitors of aspartate transcarbamoylase from Escherichia coli</title><author>Laing, Naomi ; Chan, William W.-C. ; Hutchinsoi, David W. ; Öberg, Bo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c551Q-6d11d1f27193cc6888ba2177903b7834c37e34e18d93bca2755fdf7e54a858563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Analytical, structural and metabolic biochemistry</topic><topic>aspartate carbamoyltransferase</topic><topic>Aspartate Carbamoyltransferase - antagonists & inhibitors</topic><topic>Aspartate transcarbamoylase</topic><topic>Aspartic Acid - analogs & derivatives</topic><topic>Aspartic Acid - pharmacology</topic><topic>ATCase</topic><topic>Binding Sites - drug effects</topic><topic>Biological and medical sciences</topic><topic>Diphosphates - analysis</topic><topic>Diphosphates - pharmacology</topic><topic>Enzyme inhibition</topic><topic>Enzymes and enzyme inhibitors</topic><topic>Escherichia coli</topic><topic>Escherichia coli - enzymology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Molecular Structure</topic><topic>n-phosphonoacetyl-L-aspartate</topic><topic>N-Pyrophosphoryl-L-aspartate</topic><topic>PALA</topic><topic>Phosphonoacetic Acid - analogs & derivatives</topic><topic>Phosphonoacetic Acid - pharmacology</topic><topic>phosphonoacetyl-L-aspartate</topic><topic>Structure-Activity Relationship</topic><topic>Sulfhydryl Compounds - analysis</topic><topic>Transferases</topic><topic>Transition state</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Laing, Naomi</creatorcontrib><creatorcontrib>Chan, William W.-C.</creatorcontrib><creatorcontrib>Hutchinsoi, David W.</creatorcontrib><creatorcontrib>Öberg, Bo</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 3</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Laing, Naomi</au><au>Chan, William W.-C.</au><au>Hutchinsoi, David W.</au><au>Öberg, Bo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phosphorus-containing inhibitors of aspartate transcarbamoylase from Escherichia coli</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>1990-01-29</date><risdate>1990</risdate><volume>260</volume><issue>2</issue><spage>206</spage><epage>208</epage><pages>206-208</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><coden>FEBLAL</coden><abstract>A tetrahedral intermediate is the prominent feature of the generally accepted mechanism for aspartate transcarbamoylase. We have synthesized
N-pyrophosphoryl-L-aspartate as a charged analogue of the postulated intermediate. Surprisingly, its affinity for the enzyme from
Escherichia coli was substantially lower than that of the previously known inhibitor phosphonoacetyl-L-aspartate which contained a trigonal carbonyl group. Similar results were obtained with the corresponding mercaptosuccinate derivatives. We also tested a number of new pyrophosphate analogues as inhibitors. Our results cast doubt on some aspects of the current model for the mechanism of this enzyme.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>2153584</pmid><doi>10.1016/0014-5793(90)80104-Q</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ScienceDirect Journals (5 years ago - present); Alma/SFX Local Collection |
| subjects | Analytical, structural and metabolic biochemistry aspartate carbamoyltransferase Aspartate Carbamoyltransferase - antagonists & inhibitors Aspartate transcarbamoylase Aspartic Acid - analogs & derivatives Aspartic Acid - pharmacology ATCase Binding Sites - drug effects Biological and medical sciences Diphosphates - analysis Diphosphates - pharmacology Enzyme inhibition Enzymes and enzyme inhibitors Escherichia coli Escherichia coli - enzymology Fundamental and applied biological sciences. Psychology Magnetic Resonance Spectroscopy Molecular Structure n-phosphonoacetyl-L-aspartate N-Pyrophosphoryl-L-aspartate PALA Phosphonoacetic Acid - analogs & derivatives Phosphonoacetic Acid - pharmacology phosphonoacetyl-L-aspartate Structure-Activity Relationship Sulfhydryl Compounds - analysis Transferases Transition state |
| title | Phosphorus-containing inhibitors of aspartate transcarbamoylase from Escherichia coli |
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