{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T23:03:33Z","timestamp":1768431813113,"version":"3.49.0"},"reference-count":55,"publisher":"Proceedings of the National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,1,12]]},"abstract":"<jats:p>\n            In many Gram-negative pathogens, their virulent behavior is regulated by quorum sensing, in which diffusible signals such as\n            <jats:italic>N<\/jats:italic>\n            -acyl homoserine lactones (AHLs) act as chemical messaging compounds. Enzymatic degradation of these diffusible signals by, e.g., lactonases or amidohydrolases abolishes AHL regulated virulence, a process known as quorum quenching. Here we report the first crystal structure of an AHL amidohydrolase, the AHL acylase PvdQ from\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            . PvdQ has a typical \u03b1\/\u03b2 heterodimeric Ntn-hydrolase fold, similar to penicillin G acylase and cephalosporin acylase. However, it has a distinct, unusually large, hydrophobic binding pocket, ideally suited to recognize C12 fatty acid-like chains of AHLs. Binding of a C12 fatty acid or a 3-oxo-C12 fatty acid induces subtle conformational changes to accommodate the aliphatic chain. Furthermore, the structure of a covalent ester intermediate identifies Ser\u03b21 as the nucleophile and Asn\u03b2269 and Val\u03b270 as the oxyanion hole residues in the AHL degradation process. Our structures show the versatility of the Ntn-hydrolase scaffold and can serve as a structural paradigm for Ntn-hydrolases with similar substrate preference. Finally, the quorum-quenching capabilities of PvdQ may be utilized to suppress the quorum-sensing machinery of pathogens.\n          <\/jats:p>","DOI":"10.1073\/pnas.0911839107","type":"journal-article","created":{"date-parts":[[2009,12,23]],"date-time":"2009-12-23T02:09:29Z","timestamp":1261534169000},"page":"686-691","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":134,"title":["The quorum-quenching\n            <i>N<\/i>\n            -acyl homoserine lactone acylase PvdQ is an Ntn-hydrolase with an unusual substrate-binding pocket"],"prefix":"10.1073","volume":"107","author":[{"given":"Marcel","family":"Bokhove","sequence":"first","affiliation":[{"name":"Laboratory of Biophysical Chemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands; and"}]},{"given":"Pol Nadal","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands"}]},{"given":"Wim J.","family":"Quax","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands"}]},{"given":"Bauke W.","family":"Dijkstra","sequence":"additional","affiliation":[{"name":"Laboratory of Biophysical Chemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands; and"}]}],"member":"341","published-online":{"date-parts":[[2009,12,22]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cell.2006.04.001","article-title":"Bacterially speaking","volume":"125","author":"Bassler BL","year":"2006","unstructured":"BL Bassler, R Losick, Bacterially speaking. Cell 125, 237\u2013246 (2006).","journal-title":"Cell"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1021\/bi00512a013","article-title":"Structural identification of autoinducer of Photobacterium fischeri luciferase","volume":"20","author":"Eberhard A","year":"1981","unstructured":"A Eberhard, et al., Structural identification of autoinducer of Photobacterium fischeri luciferase. Biochemistry 20, 2444\u20132449 (1981).","journal-title":"Biochemistry"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1073\/pnas.92.5.1490","article-title":"A second N-acylhomoserine lactone signal produced by Pseudomonas aeruginosa","volume":"92","author":"Pearson JP","year":"1995","unstructured":"JP Pearson, L Passador, BH Iglewski, EP Greenberg, A second N-acylhomoserine lactone signal produced by Pseudomonas aeruginosa. Proc Natl Acad Sci USA 92, 1490\u20131494 (1995).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/j.1574-6976.2001.tb00583.x","article-title":"Quorum-sensing in Gram-negative bacteria","volume":"25","author":"Whitehead NA","year":"2001","unstructured":"NA Whitehead, et al., Quorum-sensing in Gram-negative bacteria. FEMS Microbiol Rev 25, 365\u2013404 (2001).","journal-title":"FEMS Microbiol Rev"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/35081101","article-title":"Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase","volume":"411","author":"Dong YH","year":"2001","unstructured":"YH Dong, et al., Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase. Nature 411, 813\u2013817 (2001).","journal-title":"Nature"},{"key":"e_1_3_4_6_2","first-page":"101","article-title":"Quorum sensing and quorum-quenching enzymes","volume":"43","author":"Dong YH","year":"2005","unstructured":"YH Dong, LH Zhang, Quorum sensing and quorum-quenching enzymes. J Microbiol 43, 101\u2013109 (2005).","journal-title":"J Microbiol"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0168-6496(03)00125-9","article-title":"Degradation of pathogen quorum-sensing molecules by soil bacteria: A preventive and curative biological control mechanism","volume":"45","author":"Molina L","year":"2003","unstructured":"L Molina, et al., Degradation of pathogen quorum-sensing molecules by soil bacteria: A preventive and curative biological control mechanism. FEMS Microbiol Ecol 45, 71\u201381 (2003).","journal-title":"FEMS Microbiol Ecol"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s10096-008-0489-3","article-title":"Therapeutic frontiers: Preventing and treating infectious diseases by inhibiting bacterial quorum sensing","volume":"27","author":"Martin CA","year":"2008","unstructured":"CA Martin, AD Hoven, AM Cook, Therapeutic frontiers: Preventing and treating infectious diseases by inhibiting bacterial quorum sensing. Eur J Clin Microbiol 27, 635\u2013642 (2008).","journal-title":"Eur J Clin Microbiol"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"11882","DOI":"10.1073\/pnas.0505255102","article-title":"Three-dimensional structure of the quorum-quenching N-acyl homoserine lactone hydrolase from Bacillus thuringiensis","volume":"102","author":"Liu D","year":"2005","unstructured":"D Liu, et al., Three-dimensional structure of the quorum-quenching N-acyl homoserine lactone hydrolase from Bacillus thuringiensis. Proc Natl Acad Sci USA 102, 11882\u201311887 (2005).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"17606","DOI":"10.1073\/pnas.0504996102","article-title":"The molecular structure and catalytic mechanism of a quorum-quenching N-acyl-L-homoserine lactone hydrolase","volume":"102","author":"Kim MH","year":"2005","unstructured":"MH Kim, et al., The molecular structure and catalytic mechanism of a quorum-quenching N-acyl-L-homoserine lactone hydrolase. Proc Natl Acad Sci USA 102, 17606\u201317611 (2005).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"7706","DOI":"10.1021\/bi800368y","article-title":"Mechanism of the quorum-quenching lactonase (AiiA) from Bacillus thuringiensis. 1. Product-bound structures","volume":"47","author":"Liu D","year":"2008","unstructured":"D Liu, et al., Mechanism of the quorum-quenching lactonase (AiiA) from Bacillus thuringiensis. 1. Product-bound structures. Biochemistry 47, 7706\u20137714 (2008).","journal-title":"Biochemistry"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"5941","DOI":"10.1128\/AEM.69.10.5941-5949.2003","article-title":"Utilization of acyl-homoserine lactone quorum signals for growth by a soil pseudomonad and Pseudomonas aeruginosa PAO1","volume":"69","author":"Huang JJ","year":"2003","unstructured":"JJ Huang, JI Han, LH Zhang, JR Leadbetter, Utilization of acyl-homoserine lactone quorum signals for growth by a soil pseudomonad and Pseudomonas aeruginosa PAO1. Appl Environ Microbiol 69, 5941\u20135949 (2003).","journal-title":"Appl Environ Microbiol"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1128\/IAI.74.3.1673-1682.2006","article-title":"Quorum quenching by an N-acyl-homoserine lactone acylase from Pseudomonas aeruginosa PAO1","volume":"74","author":"Sio CF","year":"2006","unstructured":"CF Sio, et al., Quorum quenching by an N-acyl-homoserine lactone acylase from Pseudomonas aeruginosa PAO1. Infect Immun 74, 1673\u20131682 (2006).","journal-title":"Infect Immun"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"4891","DOI":"10.1128\/AAC.00380-09","article-title":"Quorum quenching acylase reduces the virulence of Pseudomonas aeruginosa in a Caenorhabditis elegans infection model","volume":"53","author":"Papaioannou E","year":"2009","unstructured":"E Papaioannou, et al., Quorum quenching acylase reduces the virulence of Pseudomonas aeruginosa in a Caenorhabditis elegans infection model. Antimicrob Agents Chemother 53, 4891\u20134897 (2009).","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.tim.2006.11.004","article-title":"Pyoverdine siderophores: From biogenesis to biosignificance","volume":"15","author":"Visca P","year":"2007","unstructured":"P Visca, F Imperi, IL Lamont, Pyoverdine siderophores: From biogenesis to biosignificance. Trends Microbiol 15, 22\u201330 (2007).","journal-title":"Trends Microbiol"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1099\/00221287-107-2-329","article-title":"Role of Pyoverdinepf, the iron-binding fluorescent pigment of Pseudomonas fluorescens, in iron transport","volume":"107","author":"Meyer JM","year":"1978","unstructured":"JM Meyer, JM Hornsperger, Role of Pyoverdinepf, the iron-binding fluorescent pigment of Pseudomonas fluorescens, in iron transport. J Gen Microbiol 107, 329\u2013331 (1978).","journal-title":"J Gen Microbiol"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1046\/j.1365-2958.2002.03084.x","article-title":"GeneChip expression analysis of the iron starvation response in Pseudomonas aeruginosa: identification of novel pyoverdine biosynthesis genes","volume":"45","author":"Ochsner UA","year":"2002","unstructured":"UA Ochsner, PJ Wilderman, AI Vasil, ML Vasil, GeneChip expression analysis of the iron starvation response in Pseudomonas aeruginosa: identification of novel pyoverdine biosynthesis genes. Mol Microbiol 45, 1277\u20131287 (2002).","journal-title":"Mol Microbiol"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/373264a0","article-title":"Penicillin acylase has a single-amino-acid catalytic center","volume":"373","author":"Duggleby HJ","year":"1995","unstructured":"HJ Duggleby, et al., Penicillin acylase has a single-amino-acid catalytic center. Nature 373, 264\u2013268 (1995).","journal-title":"Nature"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/S0969-2126(00)00505-0","article-title":"The 2.0 A crystal structure of cephalosporin acylase","volume":"8","author":"Kim Y","year":"2000","unstructured":"Y Kim, et al., The 2.0 A crystal structure of cephalosporin acylase. Structure 8, 1059\u20131068 (2000).","journal-title":"Structure"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1126\/science.7725107","article-title":"Proteasome from Thermoplasma acidophilum: A threonine protease","volume":"268","author":"Seemuller E","year":"1995","unstructured":"E Seemuller, et al., Proteasome from Thermoplasma acidophilum: A threonine protease. Science 268, 579\u2013582 (1995).","journal-title":"Science"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"15549","DOI":"10.1074\/jbc.271.26.15549","article-title":"Structure and function of the glutamine phosphoribosylpyrophosphate amidotransferase glutamine site and communication with the phosphoribosylpyrophosphate site","volume":"271","author":"Kim JH","year":"1996","unstructured":"JH Kim, et al., Structure and function of the glutamine phosphoribosylpyrophosphate amidotransferase glutamine site and communication with the phosphoribosylpyrophosphate site. J Biol Chem 271, 15549\u201315557 (1996).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1110\/ps.9.12.2329","article-title":"Structural comparison of Ntn-hydrolases","volume":"9","author":"Oinonen C","year":"2000","unstructured":"C Oinonen, J Rouvinen, Structural comparison of Ntn-hydrolases. Protein Sci 9, 2329\u20132337 (2000).","journal-title":"Protein Sci"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"D419","DOI":"10.1093\/nar\/gkm993","article-title":"Data growth and its impact on the SCOP database: New developments","volume":"36","author":"Andreeva A","year":"2007","unstructured":"A Andreeva, et al., Data growth and its impact on the SCOP database: New developments. Nucleic Acids Res 36, D419\u2013425 (2007).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1093\/bioinformatics\/btn507","article-title":"Searching protein structure databases with DaliLite v.3","volume":"24","author":"Holm L","year":"2008","unstructured":"L Holm, S Kaariainen, P Rosenstrom, A Schenkel, Searching protein structure databases with DaliLite v.3. Bioinformatics 24, 2780\u20132781 (2008).","journal-title":"Bioinformatics"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/8213","article-title":"Penicillin V acylase crystal structure reveals new Ntn-hydrolase family members","volume":"6","author":"Suresh CG","year":"1999","unstructured":"CG Suresh, et al., Penicillin V acylase crystal structure reveals new Ntn-hydrolase family members. Nat Struct Biol 6, 414\u2013416 (1999).","journal-title":"Nat Struct Biol"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/386463a0","article-title":"Structure of 20S proteasome from yeast at 2.4 A resolution","volume":"386","author":"Groll M","year":"1997","unstructured":"M Groll, et al., Structure of 20S proteasome from yeast at 2.4 A resolution. Nature 386, 463\u2013471 (1997).","journal-title":"Nature"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1146\/annurev.biochem.72.121801.161459","article-title":"Protein disulfide bond formation in prokaryotes","volume":"72","author":"Kadokura H","year":"2003","unstructured":"H Kadokura, F Katzen, J Beckwith, Protein disulfide bond formation in prokaryotes. Annu Rev Biochem 72, 111\u2013135 (2003).","journal-title":"Annu Rev Biochem"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul SF","year":"1990","unstructured":"SF Altschul, et al., Basic local alignment search tool. J Mol Biol 215, 403\u2013410 (1990).","journal-title":"J Mol Biol"},{"key":"e_1_3_4_29_2","first-page":"D190","article-title":"The Universal Protein Resource (UniProt)","volume":"36","year":"2008","unstructured":", The Universal Protein Resource (UniProt). Nucleic Acids Res 36, D190\u2013195 (2008).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1107\/S0108767386099622","article-title":"Improved Fourier coefficients for maps using phases from partial structures with errors","volume":"42","author":"Read R","year":"1986","unstructured":"R Read, Improved Fourier coefficients for maps using phases from partial structures with errors. Acta Crystallogr A 42, 140\u2013149 (1986).","journal-title":"Acta Crystallogr A"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1093\/protein\/13.12.857","article-title":"Characterization of the beta-lactam binding site of penicillin acylase of Escherichia coli by structural and site-directed mutagenesis studies","volume":"13","author":"Alkema WB","year":"2000","unstructured":"WB Alkema, et al., Characterization of the beta-lactam binding site of penicillin acylase of Escherichia coli by structural and site-directed mutagenesis studies. Protein Eng 13, 857\u2013863 (2000).","journal-title":"Protein Eng"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"6471","DOI":"10.1073\/pnas.0511020103","article-title":"Crystal structures of gamma-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate","volume":"103","author":"Okada T","year":"2006","unstructured":"T Okada, et al., Crystal structures of gamma-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate. Proc Natl Acad Sci USA 103, 6471\u20136476 (2006).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/378416a0","article-title":"A protein catalytic framework with an N-terminal nucleophile is capable of self-activation","volume":"378","author":"Brannigan JA","year":"1995","unstructured":"JA Brannigan, et al., A protein catalytic framework with an N-terminal nucleophile is capable of self-activation. Nature 378, 416\u2013419 (1995).","journal-title":"Nature"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1126\/science.8197456","article-title":"Structure of the allosteric regulatory enzyme of purine biosynthesis","volume":"264","author":"Smith JL","year":"1994","unstructured":"JL Smith, et al., Structure of the allosteric regulatory enzyme of purine biosynthesis. Science 264, 1427\u20131433 (1994).","journal-title":"Science"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"5378","DOI":"10.1128\/AEM.00452-07","article-title":"Newly discovered penicillin acylase activity of aculeacin A acylase from Actinoplanes utahensis","volume":"73","author":"Torres-Bacete J","year":"2007","unstructured":"J Torres-Bacete, et al., Newly discovered penicillin acylase activity of aculeacin A acylase from Actinoplanes utahensis. Appl Environ Microbiol 73, 5378\u20135381 (2007).","journal-title":"Appl Environ Microbiol"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.jbiotec.2006.12.017","article-title":"Cloning and characterization of penicillin V acylase from Streptomyces mobaraensis","volume":"128","author":"Zhang D","year":"2007","unstructured":"D Zhang, et al., Cloning and characterization of penicillin V acylase from Streptomyces mobaraensis. J Biotechnol 128, 788\u2013800 (2007).","journal-title":"J Biotechnol"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1128\/AEM.72.2.1190-1197.2006","article-title":"Identification of QuiP, the product of gene PA1032, as the second acyl-homoserine lactone acylase of Pseudomonas aeruginosa PAO1","volume":"72","author":"Huang JJ","year":"2006","unstructured":"JJ Huang, A Petersen, M Whiteley, JR Leadbetter, Identification of QuiP, the product of gene PA1032, as the second acyl-homoserine lactone acylase of Pseudomonas aeruginosa PAO1. Appl Environ Microbiol 72, 1190\u20131197 (2006).","journal-title":"Appl Environ Microbiol"},{"key":"e_1_3_4_38_2","article-title":"The role of PvdQ in Pseudomonas aeruginosa virulence under iron limiting conditions","author":"Nadal Jimenez P","year":"2009","unstructured":"P Nadal Jimenez, et al., The role of PvdQ in Pseudomonas aeruginosa virulence under iron limiting conditions. Microbiology+, doi:10.1099\/mic.0.030973-0. (2009).","journal-title":"Microbiology+"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.ab.2006.07.027","article-title":"Thermofluor-based high-throughput stability optimization of proteins for structural studies","volume":"357","author":"Ericsson UB","year":"2006","unstructured":"UB Ericsson, et al., Thermofluor-based high-throughput stability optimization of proteins for structural studies. Anal Biochem 357, 289\u2013298 (2006).","journal-title":"Anal Biochem"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1107\/S0021889893005588","article-title":"Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants","volume":"26","author":"Kabsch W","year":"1993","unstructured":"W Kabsch, Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants. J Appl Crystallogr 26, 795\u2013800 (1993).","journal-title":"J Appl Crystallogr"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1107\/S0907444905036693","article-title":"Scaling and assessment of data quality","volume":"62","author":"Evans P","year":"2006","unstructured":"P Evans, Scaling and assessment of data quality. Acta Crystallogr D 62, 72\u201382 (2006).","journal-title":"Acta Crystallogr D"},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1107\/S0907444905001617","article-title":"Likelihood-enhanced fast translation functions","volume":"61","author":"McCoy AJ","year":"2005","unstructured":"AJ McCoy, RW Grosse-Kunstleve, LC Storoni, RJ Read, Likelihood-enhanced fast translation functions. Acta Crystallogr D 61, 458\u2013464 (2005).","journal-title":"Acta Crystallogr D"},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1107\/S0907444994003112","article-title":"The CCP4 suite: Programs for protein crystallography","volume":"50","year":"1994","unstructured":", The CCP4 suite: Programs for protein crystallography. Acta Crystallogr D 50, 760\u2013763 (1994).","journal-title":"Acta Crystallogr D"},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1006\/jmbi.2000.4105","article-title":"Structure of a slow processing precursor penicillin acylase from Escherichia coli reveals the linker peptide blocking the active-site cleft","volume":"302","author":"Hewitt L","year":"2000","unstructured":"L Hewitt, et al., Structure of a slow processing precursor penicillin acylase from Escherichia coli reveals the linker peptide blocking the active-site cleft. J Mol Biol 302, 887\u2013898 (2000).","journal-title":"J Mol Biol"},{"key":"e_1_3_4_45_2","first-page":"2823","article-title":"Precursor structure of cephalosporin acylase. Insights into autoproteolytic activation in a new N-terminal hydrolase family","volume":"277","author":"Kim Y","year":"2002","unstructured":"Y Kim, S Kim, TN Earnest, WGJ Hol, Precursor structure of cephalosporin acylase. Insights into autoproteolytic activation in a new N-terminal hydrolase family. J Biol Chem 277, 2823\u20132829 (2002).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"W284","DOI":"10.1093\/nar\/gki418","article-title":"FFAS03: a server for profile\u2013profile sequence alignments","volume":"33","author":"Jaroszewski L","year":"2005","unstructured":"L Jaroszewski, et al., FFAS03: a server for profile\u2013profile sequence alignments. Nucleic Acids Res 33, W284\u2013288 (2005).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1110\/ps.03154503","article-title":"A graph-theory algorithm for rapid protein side-chain prediction","volume":"12","author":"Canutescu AA","year":"2003","unstructured":"AA Canutescu, AA Shelenkov, RL Dunbrack, A graph-theory algorithm for rapid protein side-chain prediction. Protein Sci 12, 2001\u20132014 (2003).","journal-title":"Protein Sci"},{"key":"e_1_3_4_48_2","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1107\/S0909049503023938","article-title":"SOLVE and RESOLVE: Automated structure solution, density modification and model building","volume":"11","author":"Terwilliger T","year":"2004","unstructured":"T Terwilliger, SOLVE and RESOLVE: Automated structure solution, density modification and model building. J Synchrotron Radiat 11, 49\u201352 (2004).","journal-title":"J Synchrotron Radiat"},{"key":"e_1_3_4_49_2","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: Model-building tools for molecular graphics","volume":"60","author":"Emsley P","year":"2004","unstructured":"P Emsley, K Cowtan, Coot: Model-building tools for molecular graphics. Acta Crystallogr D 60, 2126\u20132132 (2004).","journal-title":"Acta Crystallogr D"},{"key":"e_1_3_4_50_2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0076-6879(03)74011-7","article-title":"ARP\/wARP and automatic interpretation of protein electron density maps","volume":"374","author":"Morris RJ","year":"2003","unstructured":"RJ Morris, A Perrakis, VS Lamzin, ARP\/wARP and automatic interpretation of protein electron density maps. Method Enzymol 374, 229\u2013244 (2003).","journal-title":"Method Enzymol"},{"key":"e_1_3_4_51_2","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/S0076-6879(03)74014-2","article-title":"Macromolecular TLS refinement in REFMAC at moderate resolutions","volume":"374","author":"Winn MD","year":"2003","unstructured":"MD Winn, GN Murshudov, MZ Papiz, Macromolecular TLS refinement in REFMAC at moderate resolutions. Methods Enzymol 374, 300\u2013321 (2003).","journal-title":"Methods Enzymol"},{"key":"e_1_3_4_52_2","doi-asserted-by":"crossref","first-page":"W375","DOI":"10.1093\/nar\/gkm216","article-title":"MolProbity: All-atom contacts and structure validation for proteins and nucleic acids","volume":"35","author":"Davis IW","year":"2007","unstructured":"IW Davis, et al., MolProbity: All-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res 35, W375\u2013383 (2007).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_53_2","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1107\/S0907444993011333","article-title":"Detection, delineation, measurement and display of cavities in macromolecular structures","volume":"50","author":"Kleywegt GJ","year":"1994","unstructured":"GJ Kleywegt, TA Jones, Detection, delineation, measurement and display of cavities in macromolecular structures. Acta Crystallogr D 50, 178\u2013185 (1994).","journal-title":"Acta Crystallogr D"},{"key":"e_1_3_4_54_2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0263-7855(93)87010-3","article-title":"The molecular surface package","volume":"11","author":"Connolly ML","year":"1993","unstructured":"ML Connolly, The molecular surface package. J Mol Graphics 11, 139\u2013141 (1993).","journal-title":"J Mol Graphics"},{"key":"e_1_3_4_55_2","volume-title":"The PyMOL Molecular Graphics System","author":"Delano WL","year":"2002","unstructured":"WL Delano The PyMOL Molecular Graphics System (DeLano Scientific LLC, Palo Alto, CA, USA, 2002)."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0911839107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T06:49:37Z","timestamp":1654584577000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0911839107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12,22]]},"references-count":55,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2010,1,12]]}},"alternative-id":["10.1073\/pnas.0911839107"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0911839107","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,12,22]]},"assertion":[{"value":"2009-12-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}