Structural basis for a reciprocating mechanism of negative cooperativity in dimeric phosphagen kinase activity
ABSTRACT Phosphagen kinase (PK) family members catalyze the reversible phosphoryl transfer between phosphagen and ADP to reserve or release energy in cell energy metabolism. The structures of classic quaternary complexes of dimeric creatine kinase (CK) revealed asymmetric ligand binding states of tw...
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Phosphagen kinase (PK) family members catalyze the reversible phosphoryl transfer between phosphagen and ADP to reserve or release energy in cell energy metabolism. The structures of classic quaternary complexes of dimeric creatine kinase (CK) revealed asymmetric ligand binding states of two protomers, but the significance and mechanism remain unclear. To understand this negative cooperativity further, we determined the first structure of dimeric arginine kinase (dAK), another PK family member, at 1.75 A, as well as the structure of its ternary complex with AMPPNP and arginine. Further structural analysis shows that the ligand‐free protomer in a ligand‐bound dimer opens more widely than the protomers in a ligand‐free dimer, which leads to three different states of a dAK protomer. The unexpected allostery of the ligand‐free protomer in a ligand‐bound dimer should be relayed from the ligand‐binding‐induced allostery of its adjacent protomer. Mutations that weaken the inter‐protomer connections dramatically reduced the catalytic activities of dAK, indicating the importance of the allosteric propagation mediated by the homodimer interface. These results suggest a reciprocating mechanism of dimeric PK, which is shared by other ATP related oligomeric enzymes, e.g., ATP synthase.—Wu, X., Ye, S., Guo, S., Yan, W., Bartlam, M., Rao, Z. Structural basis for a reciprocating mechanism of negative cooperativity in dimeric phosphagen kinase activity. FASEB J. 24, 242–252 (2010). www.fasebj.org |
| doi_str_mv | 10.1096/fj.09-140194 |
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Phosphagen kinase (PK) family members catalyze the reversible phosphoryl transfer between phosphagen and ADP to reserve or release energy in cell energy metabolism. The structures of classic quaternary complexes of dimeric creatine kinase (CK) revealed asymmetric ligand binding states of two protomers, but the significance and mechanism remain unclear. To understand this negative cooperativity further, we determined the first structure of dimeric arginine kinase (dAK), another PK family member, at 1.75 A, as well as the structure of its ternary complex with AMPPNP and arginine. Further structural analysis shows that the ligand‐free protomer in a ligand‐bound dimer opens more widely than the protomers in a ligand‐free dimer, which leads to three different states of a dAK protomer. The unexpected allostery of the ligand‐free protomer in a ligand‐bound dimer should be relayed from the ligand‐binding‐induced allostery of its adjacent protomer. Mutations that weaken the inter‐protomer connections dramatically reduced the catalytic activities of dAK, indicating the importance of the allosteric propagation mediated by the homodimer interface. These results suggest a reciprocating mechanism of dimeric PK, which is shared by other ATP related oligomeric enzymes, e.g., ATP synthase.—Wu, X., Ye, S., Guo, S., Yan, W., Bartlam, M., Rao, Z. Structural basis for a reciprocating mechanism of negative cooperativity in dimeric phosphagen kinase activity. FASEB J. 24, 242–252 (2010). www.fasebj.org</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.09-140194</identifier><identifier>PMID: 19783784</identifier><language>eng</language><publisher>United States</publisher><subject>Adenylyl Imidodiphosphate - chemistry ; Adenylyl Imidodiphosphate - metabolism ; Amino Acid Sequence ; Animals ; ARGININE ; arginine kinase ; Arginine Kinase - chemistry ; Arginine Kinase - genetics ; Arginine Kinase - metabolism ; BASIC BIOLOGICAL SCIENCES ; Catalytic Domain - genetics ; CREATINE ; creatine kinase ; Creatine Kinase - chemistry ; Creatine Kinase - metabolism ; CRYSTAL STRUCTURE ; Crystallography, X-Ray ; Dimerization ; DIMERS ; energy metabolism ; ENZYMES ; GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE ; Humans ; In Vitro Techniques ; Kinetics ; Ligands ; METABOLISM ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis ; MUTATIONS ; national synchrotron light source ; PHOSPHOTRANSFERASES ; Phosphotransferases (Nitrogenous Group Acceptor) - chemistry ; Phosphotransferases (Nitrogenous Group Acceptor) - genetics ; Phosphotransferases (Nitrogenous Group Acceptor) - metabolism ; Protein Structure, Quaternary ; Recombinant Proteins - chemistry ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; Sea Cucumbers - enzymology ; Sea Cucumbers - genetics ; Sequence Deletion ; Sequence Homology, Amino Acid ; Static Electricity</subject><ispartof>The FASEB journal, 2010-01, Vol.24 (1), p.242-252</ispartof><rights>FASEB</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4624-e268bd75f8c02c241270eb62b08813c942aac4225ac786c6d45725ac660940f3</citedby><cites>FETCH-LOGICAL-c4624-e268bd75f8c02c241270eb62b08813c942aac4225ac786c6d45725ac660940f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.09-140194$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.09-140194$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,315,781,785,886,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19783784$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/1020165$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Xiaoai</creatorcontrib><creatorcontrib>Ye, Sheng</creatorcontrib><creatorcontrib>Guo, Shuyuan</creatorcontrib><creatorcontrib>Yan, Wupeng</creatorcontrib><creatorcontrib>Bartlam, Mark</creatorcontrib><creatorcontrib>Rao, Zihe</creatorcontrib><creatorcontrib>Brookhaven National Laboratory (BNL) National Synchrotron Light Source</creatorcontrib><title>Structural basis for a reciprocating mechanism of negative cooperativity in dimeric phosphagen kinase activity</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>ABSTRACT
Phosphagen kinase (PK) family members catalyze the reversible phosphoryl transfer between phosphagen and ADP to reserve or release energy in cell energy metabolism. The structures of classic quaternary complexes of dimeric creatine kinase (CK) revealed asymmetric ligand binding states of two protomers, but the significance and mechanism remain unclear. To understand this negative cooperativity further, we determined the first structure of dimeric arginine kinase (dAK), another PK family member, at 1.75 A, as well as the structure of its ternary complex with AMPPNP and arginine. Further structural analysis shows that the ligand‐free protomer in a ligand‐bound dimer opens more widely than the protomers in a ligand‐free dimer, which leads to three different states of a dAK protomer. The unexpected allostery of the ligand‐free protomer in a ligand‐bound dimer should be relayed from the ligand‐binding‐induced allostery of its adjacent protomer. Mutations that weaken the inter‐protomer connections dramatically reduced the catalytic activities of dAK, indicating the importance of the allosteric propagation mediated by the homodimer interface. These results suggest a reciprocating mechanism of dimeric PK, which is shared by other ATP related oligomeric enzymes, e.g., ATP synthase.—Wu, X., Ye, S., Guo, S., Yan, W., Bartlam, M., Rao, Z. Structural basis for a reciprocating mechanism of negative cooperativity in dimeric phosphagen kinase activity. FASEB J. 24, 242–252 (2010). www.fasebj.org</description><subject>Adenylyl Imidodiphosphate - chemistry</subject><subject>Adenylyl Imidodiphosphate - metabolism</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>ARGININE</subject><subject>arginine kinase</subject><subject>Arginine Kinase - chemistry</subject><subject>Arginine Kinase - genetics</subject><subject>Arginine Kinase - metabolism</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Catalytic Domain - genetics</subject><subject>CREATINE</subject><subject>creatine kinase</subject><subject>Creatine Kinase - chemistry</subject><subject>Creatine Kinase - metabolism</subject><subject>CRYSTAL STRUCTURE</subject><subject>Crystallography, X-Ray</subject><subject>Dimerization</subject><subject>DIMERS</subject><subject>energy metabolism</subject><subject>ENZYMES</subject><subject>GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Kinetics</subject><subject>Ligands</subject><subject>METABOLISM</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis</subject><subject>MUTATIONS</subject><subject>national synchrotron light source</subject><subject>PHOSPHOTRANSFERASES</subject><subject>Phosphotransferases (Nitrogenous Group Acceptor) - chemistry</subject><subject>Phosphotransferases (Nitrogenous Group Acceptor) - genetics</subject><subject>Phosphotransferases (Nitrogenous Group Acceptor) - metabolism</subject><subject>Protein Structure, Quaternary</subject><subject>Recombinant Proteins - chemistry</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - metabolism</subject><subject>Sea Cucumbers - enzymology</subject><subject>Sea Cucumbers - genetics</subject><subject>Sequence Deletion</subject><subject>Sequence Homology, Amino Acid</subject><subject>Static Electricity</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUuP0zAQgC0EYkvhxhlZXLiQZew4jn2EFeWhlTjs3i1n6rQuiR3sBNR_j6tU4sZpHvr0jWaGkNcMbhlo-aE_3YKumACmxROyYU0NlVQSnpINKM0rKWt1Q17kfAIABkw-JzdMt6puldiQ8DCnBecl2YF2NvtM-5iopcmhn1JEO_twoKPDow0-jzT2NLhD6f52FGOcXLrkfj5TH-jejy55pNMx5uloDy7Qnz7Y7KjFlXpJnvV2yO7VNW7J4-7z493X6v7Hl293H-8rFJKLynGpun3b9AqBIxeMt-A6yTtQitWoBbcWBeeNxVZJlHvRtJdCStAC-npL3q7amGdvMvq5LIAxBIezYcDLFZoCvVuhsuevxeXZjD6jGwYbXFyyaesygbEycEverySmmHNyvZmSH206F5e5PMH0JwParE8o-JureOlGt_8HX69eALUCf_zgzv-Vmd3DJ777Dvrq_gvRlJOj</recordid><startdate>201001</startdate><enddate>201001</enddate><creator>Wu, Xiaoai</creator><creator>Ye, Sheng</creator><creator>Guo, Shuyuan</creator><creator>Yan, Wupeng</creator><creator>Bartlam, Mark</creator><creator>Rao, Zihe</creator><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>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>201001</creationdate><title>Structural basis for a reciprocating mechanism of negative cooperativity in dimeric phosphagen kinase activity</title><author>Wu, Xiaoai ; Ye, Sheng ; Guo, Shuyuan ; Yan, Wupeng ; Bartlam, Mark ; Rao, Zihe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4624-e268bd75f8c02c241270eb62b08813c942aac4225ac786c6d45725ac660940f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adenylyl Imidodiphosphate - chemistry</topic><topic>Adenylyl Imidodiphosphate - metabolism</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>ARGININE</topic><topic>arginine kinase</topic><topic>Arginine Kinase - chemistry</topic><topic>Arginine Kinase - genetics</topic><topic>Arginine Kinase - metabolism</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>Catalytic Domain - genetics</topic><topic>CREATINE</topic><topic>creatine kinase</topic><topic>Creatine Kinase - chemistry</topic><topic>Creatine Kinase - metabolism</topic><topic>CRYSTAL STRUCTURE</topic><topic>Crystallography, X-Ray</topic><topic>Dimerization</topic><topic>DIMERS</topic><topic>energy metabolism</topic><topic>ENZYMES</topic><topic>GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Kinetics</topic><topic>Ligands</topic><topic>METABOLISM</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis</topic><topic>MUTATIONS</topic><topic>national synchrotron light source</topic><topic>PHOSPHOTRANSFERASES</topic><topic>Phosphotransferases (Nitrogenous Group Acceptor) - chemistry</topic><topic>Phosphotransferases (Nitrogenous Group Acceptor) - genetics</topic><topic>Phosphotransferases (Nitrogenous Group Acceptor) - metabolism</topic><topic>Protein Structure, Quaternary</topic><topic>Recombinant Proteins - chemistry</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - metabolism</topic><topic>Sea Cucumbers - enzymology</topic><topic>Sea Cucumbers - genetics</topic><topic>Sequence Deletion</topic><topic>Sequence Homology, Amino Acid</topic><topic>Static Electricity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Xiaoai</creatorcontrib><creatorcontrib>Ye, Sheng</creatorcontrib><creatorcontrib>Guo, Shuyuan</creatorcontrib><creatorcontrib>Yan, Wupeng</creatorcontrib><creatorcontrib>Bartlam, Mark</creatorcontrib><creatorcontrib>Rao, Zihe</creatorcontrib><creatorcontrib>Brookhaven National Laboratory (BNL) National Synchrotron Light Source</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Xiaoai</au><au>Ye, Sheng</au><au>Guo, Shuyuan</au><au>Yan, Wupeng</au><au>Bartlam, Mark</au><au>Rao, Zihe</au><aucorp>Brookhaven National Laboratory (BNL) National Synchrotron Light Source</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural basis for a reciprocating mechanism of negative cooperativity in dimeric phosphagen kinase activity</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2010-01</date><risdate>2010</risdate><volume>24</volume><issue>1</issue><spage>242</spage><epage>252</epage><pages>242-252</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>ABSTRACT
Phosphagen kinase (PK) family members catalyze the reversible phosphoryl transfer between phosphagen and ADP to reserve or release energy in cell energy metabolism. The structures of classic quaternary complexes of dimeric creatine kinase (CK) revealed asymmetric ligand binding states of two protomers, but the significance and mechanism remain unclear. To understand this negative cooperativity further, we determined the first structure of dimeric arginine kinase (dAK), another PK family member, at 1.75 A, as well as the structure of its ternary complex with AMPPNP and arginine. Further structural analysis shows that the ligand‐free protomer in a ligand‐bound dimer opens more widely than the protomers in a ligand‐free dimer, which leads to three different states of a dAK protomer. The unexpected allostery of the ligand‐free protomer in a ligand‐bound dimer should be relayed from the ligand‐binding‐induced allostery of its adjacent protomer. Mutations that weaken the inter‐protomer connections dramatically reduced the catalytic activities of dAK, indicating the importance of the allosteric propagation mediated by the homodimer interface. These results suggest a reciprocating mechanism of dimeric PK, which is shared by other ATP related oligomeric enzymes, e.g., ATP synthase.—Wu, X., Ye, S., Guo, S., Yan, W., Bartlam, M., Rao, Z. Structural basis for a reciprocating mechanism of negative cooperativity in dimeric phosphagen kinase activity. FASEB J. 24, 242–252 (2010). www.fasebj.org</abstract><cop>United States</cop><pmid>19783784</pmid><doi>10.1096/fj.09-140194</doi><tpages>11</tpages></addata></record> |
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| subjects | Adenylyl Imidodiphosphate - chemistry Adenylyl Imidodiphosphate - metabolism Amino Acid Sequence Animals ARGININE arginine kinase Arginine Kinase - chemistry Arginine Kinase - genetics Arginine Kinase - metabolism BASIC BIOLOGICAL SCIENCES Catalytic Domain - genetics CREATINE creatine kinase Creatine Kinase - chemistry Creatine Kinase - metabolism CRYSTAL STRUCTURE Crystallography, X-Ray Dimerization DIMERS energy metabolism ENZYMES GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE Humans In Vitro Techniques Kinetics Ligands METABOLISM Models, Molecular Molecular Sequence Data Mutagenesis MUTATIONS national synchrotron light source PHOSPHOTRANSFERASES Phosphotransferases (Nitrogenous Group Acceptor) - chemistry Phosphotransferases (Nitrogenous Group Acceptor) - genetics Phosphotransferases (Nitrogenous Group Acceptor) - metabolism Protein Structure, Quaternary Recombinant Proteins - chemistry Recombinant Proteins - genetics Recombinant Proteins - metabolism Sea Cucumbers - enzymology Sea Cucumbers - genetics Sequence Deletion Sequence Homology, Amino Acid Static Electricity |
| title | Structural basis for a reciprocating mechanism of negative cooperativity in dimeric phosphagen kinase activity |
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