{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:30:36Z","timestamp":1791012636452,"version":"4.1.0"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2003,12,29]],"date-time":"2003-12-29T00:00:00Z","timestamp":1072656000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Struct Mol Biol"],"published-print":{"date-parts":[[2004,1]]},"DOI":"10.1038\/nsmb712","type":"journal-article","created":{"date-parts":[[2003,12,29]],"date-time":"2003-12-29T12:51:07Z","timestamp":1072702267000},"page":"95-101","source":"Crossref","is-referenced-by-count":84,"title":["The structural basis of cephalosporin formation in a mononuclear ferrous enzyme"],"prefix":"10.1038","volume":"11","author":[{"given":"Karin","family":"Valeg\u00e5rd","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke C Terwisscha","family":"van Scheltinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Dubus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziella","family":"Ranghino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M","family":"\u00d6ster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janos","family":"Hajdu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inger","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2003,12,29]]},"reference":[{"key":"BFnsmb712_CR1","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1093\/jxb\/44.5.849","volume":"44","author":"AG Prescott","year":"1993","unstructured":"Prescott, A.G. A dilemma of dioxygenases (or where biochemistry and molecular biology fail to meet). J. Exp. Bot. 44, 849\u2013861 (1993).","journal-title":"J. Exp. Bot."},{"key":"BFnsmb712_CR2","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1038\/29575","volume":"394","author":"K Valeg\u00e5rd","year":"1998","unstructured":"Valeg\u00e5rd, K. et al. Structure of a cephalosporin synthase. Nature 394, 805\u2013809 (1998).","journal-title":"Nature"},{"key":"BFnsmb712_CR3","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1039\/np9880500129","volume":"5","author":"JE Baldwin","year":"1988","unstructured":"Baldwin, J.E. & Abraham, E. The biosynthesis of penicillins and cephalosporins. Nat. Prod. Rep. 5, 129\u2013145 (1988).","journal-title":"Nat. Prod. Rep."},{"key":"BFnsmb712_CR4","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/72398","volume":"7","author":"Z Zhang","year":"2000","unstructured":"Zhang, Z. et al. Structural origins of the selectivity of the trifunctional oxygenase clavaminic acid synthase. Nat. Struct. Biol. 7, 127\u2013133 (2000).","journal-title":"Nat. Struct. Biol."},{"key":"BFnsmb712_CR5","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/S0969-2126(01)00695-5","volume":"10","author":"R Wilmouth","year":"2002","unstructured":"Wilmouth, R. et al. Structure and mechanism of anthocyanidin synthase from Arabidopsis thaliana. Structure 10, 93\u2013103 (2002).","journal-title":"Structure"},{"key":"BFnsmb712_CR6","doi-asserted-by":"publisher","first-page":"5185","DOI":"10.1021\/bi016014e","volume":"41","author":"JM Elkins","year":"2002","unstructured":"Elkins, J.M. et al. X-ray crystal structure of Escherichia coli taurine\/\u03b1-ketoglutarate dioxygenase complexed to ferrous iron and substrates. Biochemistry 41, 5185\u20135192 (2002).","journal-title":"Biochemistry"},{"key":"BFnsmb712_CR7","doi-asserted-by":"publisher","first-page":"6625","DOI":"10.1046\/j.0014-2956.2001.02617.x","volume":"268","author":"IJ Clifton","year":"2001","unstructured":"Clifton, I.J., Hsueh, L.C., Baldwin, J.E., Harlos, K. & Schofield, C.J. Structure of proline 3-hydrolase. Evolution of the family of 2-oxoglutarate dependent oxygenases. Eur. J. Biochem. 268, 6625\u20136636 (2001).","journal-title":"Eur. J. Biochem."},{"key":"BFnsmb712_CR8","doi-asserted-by":"publisher","first-page":"15351","DOI":"10.1073\/pnas.202614999","volume":"99","author":"CE Dann III","year":"2002","unstructured":"Dann, C.E.. III, Bruick, R.K. & Deisenhofer, J. Structure of a factor-inhibiting hypoxia-inducible factor 1: an asparaginyl hydroxylase involved in the hypoxic response pathway. Proc. Natl. Acad. Sci. USA 99, 15351\u201315356 (2002).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnsmb712_CR9","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1074\/jbc.C200644200","volume":"278","author":"Elkins","year":"2003","unstructured":"Elkins et al. Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1\u03b1. J. Biol. Chem. 278, 1802\u20131806 (2003).","journal-title":"J. Biol. Chem."},{"key":"BFnsmb712_CR10","doi-asserted-by":"crossref","unstructured":"Lee, C., Kim, S.J., Jeong, D.G., Lee, S.M. & Ryu, S.E. Structure of human FIH-1 reveals a unique active site pocket and interaction sites for HIF-1 and von Hippel-Lindau. J. Biol. Chem. 278, 7558\u20137563.","DOI":"10.1074\/jbc.M210385200"},{"key":"BFnsmb712_CR11","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1038\/375700a0","volume":"375","author":"PL Roach","year":"1995","unstructured":"Roach, P.L. et al. Crystal structure of isopenicillin N synthase, first of a new structural family of enzymes. Nature 375, 700\u2013704 (1995).","journal-title":"Nature"},{"key":"BFnsmb712_CR12","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1111\/j.1432-1033.1997.t01-1-00625.x","volume":"250","author":"EL Hegg","year":"1997","unstructured":"Hegg, E.L. & Que, L. Jr. The 2-His-carboxylate facial triad. An emerging structural motif in mononuclear non-heme iron(II) enzymes. Eur. J. Biochem. 250, 625\u2013629 (1997).","journal-title":"Eur. J. Biochem."},{"key":"BFnsmb712_CR13","doi-asserted-by":"publisher","first-page":"3563","DOI":"10.1021\/bi962521y","volume":"36","author":"JN Barlow","year":"1997","unstructured":"Barlow, J.N., Zhang, Z.H., John, P., Baldwin, J.E. & Schofield, C.J. Inactivation of 1-aminocyclopropane-1-carboxylate oxidase involves oxidative modifications. Biochemistry 36, 3563\u20133569 (1997).","journal-title":"Biochemistry"},{"key":"BFnsmb712_CR14","doi-asserted-by":"publisher","first-page":"5126","DOI":"10.1021\/ja005879x","volume":"123","author":"A Liu","year":"2001","unstructured":"Liu, A., Ho, R.Y.N. & Que, L. Jr. Alternative reactivity of an \u03b1-ketoglutarate-dependent iron(II) oxygenase: enzyme self-hydroxylation. J. Am. Chem. Soc. 123, 5126\u20135127 (2001).","journal-title":"J. Am. Chem. Soc."},{"key":"BFnsmb712_CR15","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.1021\/bi026832m","volume":"42","author":"MJ Ryle","year":"2003","unstructured":"Ryle, M.J. et al. O2- and \u03b1-ketoglutarate-dependent tyrosyl radical formation in TauD, an \u03b1-keto acid-dependent non-heme iron dioxygenase. Biochemistry 42, 1854\u20131862 (2003).","journal-title":"Biochemistry"},{"key":"BFnsmb712_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-94-011-2928-2_1","volume-title":"The Chemistry of \u03b2-Lactams","author":"JE Baldwin","year":"1992","unstructured":"Baldwin, J.E. & Schofield, C.J. in The Chemistry of \u03b2-Lactams (ed. Page, M.I.) 1\u201378 (Blackie, London, 1992)."},{"key":"BFnsmb712_CR17","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.7164\/antibiotics.41.1694","volume":"41","author":"JE Baldwin","year":"1988","unstructured":"Baldwin, J.E. et al. Substrate specificity of cloned deacetoxycephalosporin C\/deacetylcephalosporin C synthetase. J. Antibiot. 41, 1694\u20131695 (1988).","journal-title":"J. Antibiot."},{"key":"BFnsmb712_CR18","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1007\/PL00000904","volume":"58","author":"A Dubus","year":"2001","unstructured":"Dubus, A. et al. Probing the penicillin sidechain selectivity of recombinant deacetoxycephalosporin C synthase. Cell. Mol. Life Sci. 58, 835\u2013843 (2001).","journal-title":"Cell. Mol. Life Sci."},{"key":"BFnsmb712_CR19","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/S0014-5793(02)02520-6","volume":"517","author":"Z Zhang","year":"2002","unstructured":"Zhang, Z. et al. Crystal structure of a clavaminate synthase-Fe(II)-2-oxoglutarate-substrate-NO complex: evidence for metal centred rearrangements. FEBS Lett. 517, 7\u201312 (2002).","journal-title":"FEBS Lett."},{"key":"BFnsmb712_CR20","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1038\/44400","volume":"401","author":"NI Burzlaff","year":"1999","unstructured":"Burzlaff, N.I. et al. The reaction cycle of isopenicillin N synthase observed by X-ray diffraction. Nature 401, 721\u2013724 (1999).","journal-title":"Nature"},{"key":"BFnsmb712_CR21","doi-asserted-by":"publisher","first-page":"5547","DOI":"10.1021\/bi0341096","volume":"42","author":"JR O'Brien","year":"2003","unstructured":"O'Brien, J.R., Schuller, D.J., Yang, V.S., Dillard, B.D. & Lanzilotta, W.N. Substrate-induced conformational changes in Escherichia coli taurine\/\u03b1-ketoglutarate dioxygenase and insight into the oligomeric structure. Biochemistry 42, 5547\u20135554 (2003).","journal-title":"Biochemistry"},{"key":"BFnsmb712_CR22","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1021\/cr9900275","volume":"100","author":"EI Solomon","year":"2000","unstructured":"Solomon, E.I. et al. Geometric and electronic structure\/function correlations in non-heme iron enzymes. Chem. Rev. 100, 235\u2013349 (2000).","journal-title":"Chem. Rev."},{"key":"BFnsmb712_CR23","doi-asserted-by":"publisher","first-page":"7388","DOI":"10.1021\/ja004025+","volume":"123","author":"J Zhou","year":"2001","unstructured":"Zhou, J. et al. Spectroscopic studies of substrate interactions with clavaminate synthase 2, a multifunctional \u03b1-KG-dependent non-heme iron enzyme: correlation with mechanisms and reactivities. J. Am. Chem. Soc. 123, 7388\u20137398 (2001).","journal-title":"J. Am. Chem. Soc."},{"key":"BFnsmb712_CR24","doi-asserted-by":"publisher","first-page":"7497","DOI":"10.1021\/bi030011f","volume":"42","author":"JC Price","year":"2003","unstructured":"Price, J.C., Barr, E.W., Tirupati, B., Bollinger, J.M. Jr. & Krebs, C. The first direct characterization of a high-valent iron intermediate in the reaction of an \u03b1-ketoglutarate-dependent dioxygenase: a high-spin Fe(IV) complex in taurine\/\u03b1-ketoglutarate dioxygenase (TauD) from Escherichia coli. Biochemistry 42, 7497\u20137508 (2003).","journal-title":"Biochemistry"},{"key":"BFnsmb712_CR25","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1006\/bbrc.2002.6620","volume":"292","author":"HJ Lee","year":"2002","unstructured":"Lee, H.J., Schofield, C.J. & Lloyd, M.D. Active site mutations of recombinant deacetoxycephalosporin C synthase. Biochem. Biophys. Res. Commun. 292, 66\u201370 (2002).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"BFnsmb712_CR26","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1006\/jmbi.2001.4649","volume":"308","author":"H-J Lee","year":"2001","unstructured":"Lee, H.-J. et al. Kinetic and crystallographic studies on deacetoxycephalosporin C synthase (DAOCS). J. Mol. Biol. 308, 937\u2013948 (2001).","journal-title":"J. Mol. Biol."},{"key":"BFnsmb712_CR27","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1039\/a902197c","volume":"17","author":"AG Prescott","year":"2000","unstructured":"Prescott, A.G. & Lloyd, M.D. The iron(II) and 2-oxoacid-dependent dioxygenases and their role in metabolism. Nat. Prod. Rep. 17, 367\u2013383 (2000).","journal-title":"Nat. Prod. Rep."},{"key":"BFnsmb712_CR28","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1042\/bj2220777","volume":"222","author":"CP Pang","year":"1984","unstructured":"Pang, C.P. et al. Stereochemistry of the incorporation of valine methyl groups into methylene groups in cephalosporin C. Biochem. J. 222, 777\u2013788 (1984).","journal-title":"Biochem. J."},{"key":"BFnsmb712_CR29","doi-asserted-by":"publisher","first-page":"4760","DOI":"10.1021\/ja00302a026","volume":"107","author":"CA Townsend","year":"1985","unstructured":"Townsend, C.A., Theis, A.B., Neese, A.S., Barrabee, E.B. & Poland, D. Stereochemical fate of chiral\/methyl valine in the ring expansion of penicillin N to deacetoxycephalosporin C. J. Am. Chem. Soc. 107, 4760\u20134767 (1985).","journal-title":"J. Am. Chem. Soc."},{"key":"BFnsmb712_CR30","doi-asserted-by":"publisher","first-page":"5953","DOI":"10.1016\/S0040-4020(01)81453-8","volume":"44","author":"JE Baldwin","year":"1988","unstructured":"Baldwin, J.E., Adlington, R.M., Kang, T.W., Lee, E. & Schofield, C.J. The ring expansion of penams to cephams: a possible biomimetic process. Tetrahedron 44, 5953\u20135957 (1988).","journal-title":"Tetrahedron"},{"key":"BFnsmb712_CR31","doi-asserted-by":"publisher","first-page":"11356","DOI":"10.1021\/ja992649d","volume":"121","author":"D Iwata-Reuyl","year":"1999","unstructured":"Iwata-Reuyl, D., Basak, A. & Townsend, C.A. \u03b2-Secondary kinetic isotope effects in the clavaminate synthase-catalysed oxidative cyclization of proclavaminic acid and in related azetidinone model reactions. J. Am. Chem. Soc. 121, 11356\u201311368 (1999).","journal-title":"J. Am. Chem. Soc."},{"key":"BFnsmb712_CR32","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1021\/ja981193h","volume":"121","author":"M Wu","year":"1999","unstructured":"Wu, M., Moon, H.-S. & Begley, T.P. Mechanism-based inactivation of the human prolyl-4-hydroxylase by 5-oxaproline-containing peptides: evidence for a prolyl radical intermediate. J. Am. Chem. Soc. 121, 587\u2013588 (1999).","journal-title":"J. Am. Chem. Soc."},{"key":"BFnsmb712_CR33","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1021\/ja00895a063","volume":"85","author":"RB Morin","year":"1963","unstructured":"Morin, R.B. et al. Chemistry of cephalosporin antibiotics. III. Chemical correlation of penicillin and cephalosporin antibiotics. J. Am. Chem. Soc. 85, 1896\u20131897 (1963).","journal-title":"J. Am. Chem. Soc."},{"key":"BFnsmb712_CR34","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/S0006-291X(02)00629-0","volume":"295","author":"HS Chin","year":"2002","unstructured":"Chin, H.S. & Sim, T.S. C-terminus modification of Streptomyces clavuligerus deacetoxycephalosporin C synthase improves catalysis with an expanded substrate specificity. Biochem. Biophys. Res. Commun. 295, 55\u201361 (2002).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"BFnsmb712_CR35","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/S0014-5793(03)01008-1","volume":"553","author":"A Szoke","year":"2003","unstructured":"Szoke, A., Scott, W.G. & Hajdu, J. Catalysis, evolution and life. FEBS Lett. 553, 18\u201320 (2003).","journal-title":"FEBS Lett."},{"key":"BFnsmb712_CR36","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1002\/anie.199003551","volume":"29","author":"J Retey","year":"1990","unstructured":"Retey, J. Enzymatic-reaction selectivity by negative catalysis or how do enzymes deal with highly reactive intermediates. Angew. Chem. Int. Ed. 29, 355\u2013361 (1990).","journal-title":"Angew. Chem. Int. Ed."},{"key":"BFnsmb712_CR37","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1006\/jmbi.1999.2594","volume":"287","author":"MD Lloyd","year":"1999","unstructured":"Lloyd, M.D. et al. Studies on the active site of deacetoxycephalosporin C synthase. J. Mol. Biol. 287, 943\u2013960 (1999).","journal-title":"J. Mol. Biol."},{"key":"BFnsmb712_CR38","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1107\/S0907444901014081","volume":"57","author":"AC Terwisscha van Scheltinga","year":"2001","unstructured":"Terwisscha van Scheltinga, A.C., Valeg\u00e5rd, K., Subramanian, R., Hajdu, J. & Andersson, I. Multiple isomorphous replacement on merohedral twins: structure determination of deacetoxycephalosporin C synthase. Acta Crystallogr. D 57, 1776\u20131785 (2001).","journal-title":"Acta Crystallogr. D"},{"key":"BFnsmb712_CR39","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","volume":"276","author":"Z Otwinowski","year":"1997","unstructured":"Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307\u2013326 (1997).","journal-title":"Methods Enzymol."},{"key":"BFnsmb712_CR40","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1107\/S0907444996012255","volume":"53","author":"GN Murshudov","year":"1997","unstructured":"Murshudov, G.N., Vagin, A.A. & Dodson, E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D 53, 240\u2013255 (1997).","journal-title":"Acta Crystallogr. D"},{"key":"BFnsmb712_CR41","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/978-1-4612-3374-9_13","volume-title":"Crystallographic and Modelling Methods (in Molecular Design)","author":"TA Jones","year":"1990","unstructured":"Jones, T.A., Bergdoll, M. & Kjeldgaard, M. in Crystallographic and Modelling Methods (in Molecular Design) (eds. Bugg, C. & Ealick, S.) 189\u2013190 (Springer, New York, 1990)."},{"key":"BFnsmb712_CR42","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1107\/S0907444901007697","volume":"57","author":"M Harris","year":"2001","unstructured":"Harris, M. & Jones, T.A. Molray\u2014a web interface between O and the Pov-Ray ray tracer. Acta Crystallogr. D 57, 1201\u20131203 (2001).","journal-title":"Acta Crystallogr. D"},{"key":"BFnsmb712_CR43","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1107\/S0021889891004399","volume":"24","author":"P Kraulis","year":"1991","unstructured":"Kraulis, P. MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24, 946\u2013950 (1991).","journal-title":"J. Appl. Crystallogr."},{"key":"BFnsmb712_CR44","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/S1093-3263(97)00021-1","volume":"15","author":"RM Esnouf","year":"1997","unstructured":"Esnouf, R.M. An extensively modified version of MolScript that includes greatly enhanced coloring capabilities. J. Mol. Graph. Model. 15, 132\u2013134 (1997).","journal-title":"J. Mol. Graph. Model."},{"key":"BFnsmb712_CR45","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/S0076-6879(97)77028-9","volume":"277","author":"EA Merrit","year":"1997","unstructured":"Merrit, E.A. & Bacon D.J. Raster 3D: photorealistic molecular graphics. Methods Enzymol. 277, 505\u2013524 (1997).","journal-title":"Methods Enzymol."}],"container-title":["Nature Structural & Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nsmb712.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nsmb712","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nsmb712.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:52:25Z","timestamp":1684457545000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nsmb712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,12,29]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004,1]]}},"alternative-id":["BFnsmb712"],"URL":"https:\/\/doi.org\/10.1038\/nsmb712","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1018175.206679","asserted-by":"object"}]},"ISSN":["1545-9993","1545-9985"],"issn-type":[{"value":"1545-9993","type":"print"},{"value":"1545-9985","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,12,29]]}}}