{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:30:55Z","timestamp":1787808655956,"version":"build-2784847793"},"reference-count":43,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"NIH","award":["AI090685"],"award-info":[{"award-number":["AI090685"]}]},{"name":"NIH","award":["P41 RR001081"],"award-info":[{"award-number":["P41 RR001081"]}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation (NSF)","doi-asserted-by":"crossref","award":["DBI-9871464"],"award-info":[{"award-number":["DBI-9871464"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute for General Medical Sciences (NIGMS)","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics"],"published-print":{"date-parts":[[2013,1]]},"DOI":"10.1016\/j.bbapap.2012.09.001","type":"journal-article","created":{"date-parts":[[2012,9,19]],"date-time":"2012-09-19T23:21:17Z","timestamp":1348096877000},"page":"46-52","source":"Crossref","is-referenced-by-count":11,"title":["Structure\u2013activity relationship for enantiomers of potent inhibitors of B. anthracis dihydrofolate reductase"],"prefix":"10.1016","volume":"1834","author":[{"given":"Christina R.","family":"Bourne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Wakeham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baskar","family":"Nammalwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Tseitin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip C.","family":"Bourne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther W.","family":"Barrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shankari","family":"Mylvaganam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kal","family":"Ramnarayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Bunce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Darrell","family":"Berlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Barrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bbapap.2012.09.001_bb0005","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.1176667","article-title":"Antibiotics for emerging pathogens","volume":"325","author":"Fischbach","year":"2009","journal-title":"Science"},{"key":"10.1016\/j.bbapap.2012.09.001_bb0010","doi-asserted-by":"crossref","first-page":"4447","DOI":"10.1128\/AAC.00628-07","article-title":"In vitro efficacy of new antifolates against trimethoprim-resistant Bacillus anthracis","volume":"51","author":"Barrow","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0015","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nature10388","article-title":"Antibiotic resistance is ancient","volume":"477","author":"D'Costa","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.bbapap.2012.09.001_bb0020","first-page":"17","article-title":"The antibiotic sensitivity patterns of Bacillus anthracis isolated from the Kruger National Park","volume":"58","author":"Odendaal","year":"1991","journal-title":"Onderstepoort, J. Vet. Res."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0025","volume":"OTA-ISC-559","author":"Congress","year":"1993"},{"key":"10.1016\/j.bbapap.2012.09.001_bb0030","doi-asserted-by":"crossref","first-page":"3620","DOI":"10.1128\/AAC.00377-09","article-title":"In vitro and in vivo properties of dihydrophthalazine antifolates, a novel family of antibacterial drugs","volume":"53","author":"Caspers","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0035","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1128\/AAC.01619-08","article-title":"Antistaphylococcal activity of dihydrophthalazine antifolates, a family of novel antibacterial drugs","volume":"53","author":"Clark","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0040","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1093\/jac\/dkp024","article-title":"Increased hydrophobic interactions of iclaprim with Staphylococcus aureus dihydrofolate reductase are responsible for the increase in affinity and antibacterial activity","volume":"63","author":"Oefner","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0045","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1128\/AAC.01620-07","article-title":"Antistreptococcal activity of AR-709 compared to that of other agents","volume":"52","author":"Smith","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0050","doi-asserted-by":"crossref","first-page":"5171","DOI":"10.1016\/j.bmcl.2011.07.059","article-title":"Structure-based design of new DHFR-based antibacterial agents: 7-aryl-2,4-diaminoquinazolines","volume":"21","author":"Li","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0055","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1517\/13543776.2011.587804","article-title":"Antifolate agents: a patent review (2006\u20132010)","volume":"21","author":"Wright","year":"2011","journal-title":"Expert Opin. Ther. Pat."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0060","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1128\/AAC.01666-08","article-title":"Crystal structure of Bacillus anthracis dihydrofolate reductase with the dihydrophthalazine-based trimethoprim derivative RAB1 provides a structural explanation of potency and selectivity","volume":"53","author":"Bourne","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0065","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.drup.2009.02.001","article-title":"Mutational \u2018hot-spots\u2019 in mammalian, bacterial and protozoal dihydrofolate reductases associated with antifolate resistance: sequence and structural comparison","volume":"12","author":"Volpato","year":"2009","journal-title":"Drug Resist. Updat."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0070","doi-asserted-by":"crossref","first-page":"4374","DOI":"10.1021\/jm070319v","article-title":"Crystal structure of the anthrax drug target, Bacillus anthracis dihydrofolate reductase","volume":"50","author":"Bennett","year":"2007","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0075","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/S0969-2126(94)00093-X","article-title":"The structure of Pneumocystis carinii dihydrofolate reductase to 1.9 A resolution","volume":"2","author":"Champness","year":"1994","journal-title":"Structure"},{"key":"10.1016\/j.bbapap.2012.09.001_bb0080","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1006\/jmbi.1999.3328","article-title":"Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs","volume":"295","author":"Li","year":"2000","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0085","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1021\/bi962337c","article-title":"Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence","volume":"36","author":"Sawaya","year":"1997","journal-title":"Biochemistry"},{"key":"10.1016\/j.bbapap.2012.09.001_bb0090","doi-asserted-by":"crossref","first-page":"7327","DOI":"10.1021\/jm100727t","article-title":"Targeted mutations of Bacillus anthracis dihydrofolate reductase condense complex structure\u2013activity relationships","volume":"53","author":"Beierlein","year":"2010","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0095","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.ejmech.2012.05.018","article-title":"Synthesis and biological activity of substituted 2,4-dimainopyrimidines that inhibit Bacillus anthracis","volume":"54","author":"Nammalwar","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0100","first-page":"139","volume":"90","author":"Bunce","year":"2010","journal-title":"Proc. Okla. Acad. Sci."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0105","doi-asserted-by":"crossref","first-page":"3825","DOI":"10.1128\/AAC.00361-10","article-title":"Inhibition of antibiotic-resistant Staphylococcus aureus by the broad-spectrum dihydrofolate reductase inhibitor RAB1","volume":"54","author":"Bourne","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0110","first-page":"307","article-title":"Processing of X-ray diffraction data collected in oscillation mode","volume":"276","author":"Otwinowski","year":"1997"},{"key":"10.1016\/j.bbapap.2012.09.001_bb0115","first-page":"22","article-title":"Scala","volume":"vol. 33","author":"Evans","year":"1997"},{"key":"10.1016\/j.bbapap.2012.09.001_bb0120","first-page":"41","article-title":"Processing diffraction data with Mosflm","volume":"vol. 245","author":"Leslie","year":"2007"},{"key":"10.1016\/j.bbapap.2012.09.001_bb0125","article-title":"Proteum 2 Software Suite","author":"Bruker","year":"2006"},{"key":"10.1016\/j.bbapap.2012.09.001_bb0130","series-title":"Siemens Analytical X-ray Instruments, Madison Wisconsin USA","article-title":"XPREP. Space group determination and reciprocal space plots","author":"Sheldrick","year":"1991"},{"key":"10.1016\/j.bbapap.2012.09.001_bb0135","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: a comprehensive Python-based system for macromolecular structure solution","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0140","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0145","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0150","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/bioinformatics\/15.4.327","article-title":"Automated analysis of interatomic contacts in proteins","volume":"15","author":"Sobolev","year":"1999","journal-title":"Bioinformatics"},{"key":"10.1016\/j.bbapap.2012.09.001_bb0155","doi-asserted-by":"crossref","first-page":"W116","DOI":"10.1093\/nar\/gkl282","article-title":"CASTp: computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues","volume":"34","author":"Dundas","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0160","doi-asserted-by":"crossref","first-page":"11092","DOI":"10.1021\/bi00110a011","article-title":"Investigation of the functional role of tryptophan-22 in Escherichia coli dihydrofolate reductase by site-directed mutagenesis","volume":"30","author":"Warren","year":"1991","journal-title":"Biochemistry"},{"key":"10.1016\/j.bbapap.2012.09.001_bb0165","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1107\/S0907444910041004","article-title":"Structural analysis of Pneumocystis carinii and human DHFR complexes with NADPH and a series of five potent 6-[5\u2032-(omega-carboxyalkoxy)benzyl]pyrido[2,3-d]pyrimidine derivatives","volume":"67","author":"Cody","year":"2011","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0170","unstructured":"A.K.W. Leung, L.J. Ross, S. Zywno-Van Ginkel, R.C. Reynolds, L.E. Seitz, V. Pathak, W.W. Barrow, E.L. White, W.J. Suling, J.R. Piper, D.W. Borhani, Structural basis for selective inhibition of Mycobacterium avium dihydrofolate reductase by a lipophilic antifolate, (to be published)."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0175","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jsb.2011.06.001","article-title":"Crystallographic analysis reveals a novel second binding site for trimethoprim in active site double mutants of human dihydrofolate reductase","volume":"176","author":"Cody","year":"2011","journal-title":"J. Struct. Biol."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0180","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jsb.2009.12.011","article-title":"Towards the understanding of resistance mechanisms in clinically isolated trimethoprim-resistant, methicillin-resistant Staphylococcus aureus dihydrofolate reductase","volume":"170","author":"Frey","year":"2010","journal-title":"J. Struct. Biol."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0185","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1021\/cb200124r","article-title":"Trypanosomal dihydrofolate reductase reveals natural antifolate resistance","volume":"6","author":"Vanichtanankul","year":"2011","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0190","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1021\/ja209425w","article-title":"Effects of the donor\u2013acceptor distance and dynamics on hydride tunneling in the dihydrofolate reductase catalyzed reaction","volume":"134","author":"Stojkovic","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0195","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1039\/b718519g","article-title":"Thermodynamics of stacking interactions in proteins","volume":"10","author":"Marsili","year":"2008","journal-title":"Phys. Chem. Chem. Phys."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0200","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1128\/AAC.41.11.2406","article-title":"Mutations in the dihydrofolate reductase gene of trimethoprim-resistant isolates of Streptococcus pneumoniae","volume":"41","author":"Adrian","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0205","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1128\/AAC.43.1.141","article-title":"Characterization of dihydrofolate reductase genes from trimethoprim-susceptible and trimethoprim-resistant strains of Enterococcus faecalis","volume":"43","author":"Coque","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0210","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1006\/jmbi.1996.0770","article-title":"A single amino acid substitution in Staphylococcus aureus dihydrofolate reductase determines trimethoprim resistance","volume":"266","author":"Dale","year":"1997","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.bbapap.2012.09.001_bb0215","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1128\/AAC.39.9.1920","article-title":"Cloning and characterization of a novel, plasmid-encoded trimethoprim-resistant dihydrofolate reductase from Staphylococcus haemolyticus MUR313","volume":"39","author":"Dale","year":"1995","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1570963912002051?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1570963912002051?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T22:51:42Z","timestamp":1562194302000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1570963912002051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,1]]}},"alternative-id":["S1570963912002051"],"URL":"https:\/\/doi.org\/10.1016\/j.bbapap.2012.09.001","relation":{},"ISSN":["1570-9639"],"issn-type":[{"value":"1570-9639","type":"print"}],"subject":[],"published":{"date-parts":[[2013,1]]}}}