Penam Sulfones and β-Lactamase Inhibition: SA2-13 and the Importance of the C2 Side Chain Length and Composition
Publication Date
January 16, 2014
Journal
PLOS ONE
Authors
Elizabeth A. Rodkey, Marisa L. Winkler, Christopher R. Bethel, Sundar Ram Reddy Pagadala, et al
Volume
9
Issue
1
Pages
e85892
DOI
https://dx.plos.org/10.1371/journal.pone.0085892
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0085892
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/24454944
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894197
Europe PMC
http://europepmc.org/abstract/MED/24454944
Web of Science
000330236000020
Scopus
84898662111
Mendeley
http://www.mendeley.com/research/penam-sulfones-%CE%B2lactamase-inhibition-sa213-importance-c2-side-chain-length-composition
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Mendeley | Further Information

{"title"=>"Penam sulfones and β-lactamase inhibition: SA2-13 and the importance of the C2 side chain length and composition", "type"=>"journal", "authors"=>[{"first_name"=>"Elizabeth A.", "last_name"=>"Rodkey", "scopus_author_id"=>"55232696400"}, {"first_name"=>"Marisa L.", "last_name"=>"Winkler", "scopus_author_id"=>"55360146000"}, {"first_name"=>"Christopher R.", "last_name"=>"Bethel", "scopus_author_id"=>"6603903207"}, {"first_name"=>"Sundar Ram Reddy", "last_name"=>"Pagadala", "scopus_author_id"=>"26026418200"}, {"first_name"=>"John D.", "last_name"=>"Buynak", "scopus_author_id"=>"6603935516"}, {"first_name"=>"Robert A.", "last_name"=>"Bonomo", "scopus_author_id"=>"7005121269"}, {"first_name"=>"Focco", "last_name"=>"Van Den Akker", "scopus_author_id"=>"55932216000"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"372838558", "sgr"=>"84898662111", "issn"=>"19326203", "pmid"=>"24454944", "scopus"=>"2-s2.0-84898662111", "doi"=>"10.1371/journal.pone.0085892", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"2cb23344-5aa7-3588-9610-e607424cbd69", "abstract"=>"β-Lactamases are the major reason β-lactam resistance is seen in Gram-negative bacteria. To combat this resistance mechanism, β-lactamase inhibitors are currently being developed. Presently, there are only three that are in clinical use (clavulanate, sulbactam and tazobactam). In order to address this important medical need, we explored a new inhibition strategy that takes advantage of a long-lived inhibitory trans-enamine intermediate. SA2-13 was previously synthesized and shown to have a lower k(react) than tazobactam. We investigated here the importance of the carboxyl linker length and composition by synthesizing three analogs of SA2-13 (PSR-4-157, PSR-4-155, and PSR-3-226). All SA2-13 analogs yielded higher turnover numbers and k(react) compared to SA2-13. We next demonstrated using protein crystallography that increasing the linker length by one carbon allowed for better capture of a trans-enamine intermediate; in contrast, this trans-enamine intermediate did not occur when the C2 linker length was decreased by one carbon. If the linker was altered by both shortening it and changing the carboxyl moiety into a neutral amide moiety, the stable trans-enamine intermediate in wt SHV-1 did not form; this intermediate could only be observed when a deacylation deficient E166A variant was studied. We subsequently studied SA2-13 against a relatively recently discovered inhibitor-resistant (IR) variant of SHV-1, SHV K234R. Despite the alteration in the mechanism of resistance due to the K→R change in this variant, SA2-13 was effective at inhibiting this IR enzyme and formed a trans-enamine inhibitory intermediate similar to the intermediate seen in the wt SHV-1 structure. Taken together, our data reveals that the C2 side chain linker length and composition profoundly affect the formation of the trans-enamine intermediate of penam sulfones. We also show that the design of SA2-13 derivatives offers promise against IR SHV β-lactamases that possess the K234R substitution.", "link"=>"http://www.mendeley.com/research/penam-sulfones-%CE%B2lactamase-inhibition-sa213-importance-c2-side-chain-length-composition", "reader_count"=>12, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>2, "Other"=>2, "Student > Master"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>2, "Other"=>2, "Student > Master"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>1, "Medicine and Dentistry"=>1, "Chemistry"=>3, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>3}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1349494"], "description"=>"<p>(A) Chemical structures for SA-2-13, PSR-4-157, PSR-4-155, and PSR-3-226. The ring atoms of SA2-13 are numbered to indicate the position of the C2 carboxyl linker and C3 carboxyl groups. (B) Proposed β-lactamase inhibition reaction scheme for SA2-13.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Protein interactions", "protein structure", "protein synthesis", "Biomacromolecule-ligand interactions", "drug discovery", "Small molecules", "biophysics", "Protein folding", "microbiology", "Bacterial pathogens", "Gram negative", "proteomics", "crystallography", "Drugs and devices", "Drug research and development"], "article_id"=>902656, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Elizabeth A. Rodkey", "Marisa L. Winkler", "Christopher R. Bethel", "Sundar Ram Reddy Pagadala", "John D. Buynak", "Robert A. Bonomo", "Focco van den Akker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085892.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_946_lactamase_inhibitors_/902656", "title"=>"β-lactamase inhibitors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-16 03:25:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349507"], "description"=>"<p><i>K<sub>i</sub></i> values for <i>wt</i> SHV-1 and K234R SHV versus SA2-13, clavulanate, sulbactam, and tazobactam.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Protein interactions", "protein structure", "protein synthesis", "Biomacromolecule-ligand interactions", "drug discovery", "Small molecules", "biophysics", "Protein folding", "microbiology", "Bacterial pathogens", "Gram negative", "proteomics", "crystallography", "Drugs and devices", "Drug research and development", "shv-1", "k234r", "shv"], "article_id"=>902669, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Elizabeth A. Rodkey", "Marisa L. Winkler", "Christopher R. Bethel", "Sundar Ram Reddy Pagadala", "John D. Buynak", "Robert A. Bonomo", "Focco van den Akker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085892.t003", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_K_i_values_for_wt_SHV_1_and_K234R_SHV_versus_SA2_13_clavulanate_sulbactam_and_tazobactam_/902669", "title"=>"<i>K<sub>i</sub></i> values for <i>wt</i> SHV-1 and K234R SHV versus SA2-13, clavulanate, sulbactam, and tazobactam.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-16 03:25:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349506"], "description"=>"<p>Some values were not applicable (NA) because steady-state had already been achieved when the assay with nitrocefin was started following the 30 min incubation. For these measurements recovery of full enzyme activity had already occurred.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Protein interactions", "protein structure", "protein synthesis", "Biomacromolecule-ligand interactions", "drug discovery", "Small molecules", "biophysics", "Protein folding", "microbiology", "Bacterial pathogens", "Gram negative", "proteomics", "crystallography", "Drugs and devices", "Drug research and development", "sa-2-13", "derivatives", "tazobactam"], "article_id"=>902668, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Elizabeth A. Rodkey", "Marisa L. Winkler", "Christopher R. Bethel", "Sundar Ram Reddy Pagadala", "John D. Buynak", "Robert A. Bonomo", "Focco van den Akker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085892.t002", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kinetic_parameters_for_SA_2_13_derivatives_and_tazobactam_for_comparison_/902668", "title"=>"<i>Kinetic parameters</i> for SA-2-13 derivatives and tazobactam for comparison.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-16 03:25:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349503"], "description"=>"<p>(A) Interactions of SA2-13 (green carbon ball-and-stick) covalently bound in the active site of K234R SHV (green carbon stick model). Hydrogen bonds are depicted as dashed lines. (B). Superpositioning of SA2-13 bound structures of <i>wt</i> SHV-1 (grey carbon atoms) and K234R SHV (green carbon atoms). The protein Cα atoms were used for the superpositioning.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Protein interactions", "protein structure", "protein synthesis", "Biomacromolecule-ligand interactions", "drug discovery", "Small molecules", "biophysics", "Protein folding", "microbiology", "Bacterial pathogens", "Gram negative", "proteomics", "crystallography", "Drugs and devices", "Drug research and development", "bound", "ir", "k234r"], "article_id"=>902665, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Elizabeth A. Rodkey", "Marisa L. Winkler", "Christopher R. Bethel", "Sundar Ram Reddy Pagadala", "John D. Buynak", "Robert A. Bonomo", "Focco van den Akker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085892.g007", "stats"=>{"downloads"=>0, "page_views"=>34, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SA2_13_bound_in_the_active_site_of_IR_K234R_SHV_/902665", "title"=>"SA2-13 bound in the active site of IR K234R SHV.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-16 03:25:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349501"], "description"=>"<p>|F<sub>o</sub>|-|F<sub>c</sub>| electron difference density map is contoured at 3.0σ prior to inclusion of the inhibitor in refinement.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Protein interactions", "protein structure", "protein synthesis", "Biomacromolecule-ligand interactions", "drug discovery", "Small molecules", "biophysics", "Protein folding", "microbiology", "Bacterial pathogens", "Gram negative", "proteomics", "crystallography", "Drugs and devices", "Drug research and development", "maps", "sa2-13", "bound", "k234r", "shv"], "article_id"=>902663, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Elizabeth A. Rodkey", "Marisa L. Winkler", "Christopher R. Bethel", "Sundar Ram Reddy Pagadala", "John D. Buynak", "Robert A. Bonomo", "Focco van den Akker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085892.g006", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Electron_density_maps_of_SA2_13_bound_in_the_K234R_SHV_active_site_/902663", "title"=>"Electron density maps of SA2-13 bound in the K234R SHV active site.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-16 03:25:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349500"], "description"=>"<p>(A) Interactions of PSR-4-157 in the active site of <i>wt</i> SHV-1. The C2 carboxyl-tail linker of PSR-4-157 was observed in two conformations (labeled ‘<u>1</u>’ and ‘<u>2</u>’). Hydrogen bonds with the protein are indicated by dashed lines. (B) Superposition of PSR-4-157 (cyan) and SA2-13 (grey) when bound to <i>wt</i> SHV-1. The protein Cα atoms were used for the superpositioning. (C) Interactions of the ordered PSR-4-157 fragment in the active site of the deacylation deficient E166A SHV variant. Only 6 atoms of a covalently bonded PSR-3-226 intermediate could be built into the electron density (magenta carbon atoms); the nearby HEPES buffer molecule fragment (green carbon atoms) was also included in this figure.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Protein interactions", "protein structure", "protein synthesis", "Biomacromolecule-ligand interactions", "drug discovery", "Small molecules", "biophysics", "Protein folding", "microbiology", "Bacterial pathogens", "Gram negative", "proteomics", "crystallography", "Drugs and devices", "Drug research and development", "inhibitors"], "article_id"=>902662, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Elizabeth A. Rodkey", "Marisa L. Winkler", "Christopher R. Bethel", "Sundar Ram Reddy Pagadala", "John D. Buynak", "Robert A. Bonomo", "Focco van den Akker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085892.g005", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Interactions_of_the_inhibitors_in_the_active_site_/902662", "title"=>"Interactions of the inhibitors in the active site.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-16 03:25:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349497"], "description"=>"<p>(A) |Fo|-|Fc| electron density difference map contoured at 3.0σ for PSR-4-157 prior to inclusion in refinement. The C2 carboxyl-tail linker was observed to be in two conformations. (B) |F<sub>o</sub>|-|F<sub>c</sub>| difference density for PSR-4-155 soaked <i>wt</i> SHV-1 soaked crystals revealing an absence of strong, interpretable inhibitor density. (C) |F<sub>o</sub>|-|F<sub>c</sub>| electron density difference map contoured at 3.0σ for PSR-3-226 prior to inclusion in refinement in the E166A SHV structure. Observed density reveals presence of a partially ordered PSR-3-226 fragment, right, and a HEPES buffer molecule fragment, left.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Protein interactions", "protein structure", "protein synthesis", "Biomacromolecule-ligand interactions", "drug discovery", "Small molecules", "biophysics", "Protein folding", "microbiology", "Bacterial pathogens", "Gram negative", "proteomics", "crystallography", "Drugs and devices", "Drug research and development", "maps", "inhibitors", "bound", "shv-1"], "article_id"=>902659, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Elizabeth A. Rodkey", "Marisa L. Winkler", "Christopher R. Bethel", "Sundar Ram Reddy Pagadala", "John D. Buynak", "Robert A. Bonomo", "Focco van den Akker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085892.g004", "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Electron_density_maps_for_inhibitors_bound_to_SHV_1_946_lactamase_/902659", "title"=>"Electron density maps for inhibitors bound to SHV-1 β-lactamase.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-16 03:25:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349496"], "description"=>"<p>Reaction of enzyme (E) with inhibitor (I) leading to the formation of the Michaelis complex (E:I), acylated enzyme (E-I) and breakdown of the inhibitor to product (P) with regeneration of active enzyme.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Protein interactions", "protein structure", "protein synthesis", "Biomacromolecule-ligand interactions", "drug discovery", "Small molecules", "biophysics", "Protein folding", "microbiology", "Bacterial pathogens", "Gram negative", "proteomics", "crystallography", "Drugs and devices", "Drug research and development", "enzyme", "inhibitor", "michaelis", "acylated", "breakdown", "regeneration"], "article_id"=>902658, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Elizabeth A. Rodkey", "Marisa L. Winkler", "Christopher R. Bethel", "Sundar Ram Reddy Pagadala", "John D. Buynak", "Robert A. Bonomo", "Focco van den Akker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085892.g003", "stats"=>{"downloads"=>0, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reaction_of_enzyme_E_with_inhibitor_I_leading_to_the_formation_of_the_Michaelis_complex_E_I_acylated_enzyme_E_I_and_breakdown_of_the_inhibitor_to_product_P_with_regeneration_of_active_enzyme_/902658", "title"=>"Reaction of enzyme (E) with inhibitor (I) leading to the formation of the Michaelis complex (E:I), acylated enzyme (E-I) and breakdown of the inhibitor to product (P) with regeneration of active enzyme.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-16 03:25:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349509", "https://ndownloader.figshare.com/files/1349510", "https://ndownloader.figshare.com/files/1349511"], "description"=>"<div><p>β-Lactamases are the major reason β-lactam resistance is seen in Gram-negative bacteria. To combat this resistance mechanism, β-lactamase inhibitors are currently being developed. Presently, there are only three that are in clinical use (clavulanate, sulbactam and tazobactam). In order to address this important medical need, we explored a new inhibition strategy that takes advantage of a long-lived inhibitory <i>trans</i>-enamine intermediate. SA2-13 was previously synthesized and shown to have a lower <i>k</i><sub>react</sub> than tazobactam. We investigated here the importance of the carboxyl linker length and composition by synthesizing three analogs of SA2-13 (<i>PSR-4-157, PSR-4-155, and PSR-3-226</i>). All SA2-13 analogs yielded higher turnover numbers and <i>k</i><sub>react</sub> compared to SA2-13. We next demonstrated using protein crystallography that increasing the linker length by one carbon allowed for better capture of a <i>trans</i>-enamine intermediate; in contrast, this <i>trans</i>-enamine intermediate did not occur when the C2 linker length was decreased by one carbon. If the linker was altered by both shortening it and changing the carboxyl moiety into a neutral amide moiety, the stable <i>trans</i>-enamine intermediate in <i>wt</i> SHV-1 did not form; this intermediate could only be observed when a deacylation deficient E166A variant was studied. We subsequently studied SA2-13 against a relatively recently discovered inhibitor-resistant (IR) variant of SHV-1, SHV K234R. Despite the alteration in the mechanism of resistance due to the K→R change in this variant, SA2-13 was effective at inhibiting this IR enzyme and formed a <i>trans</i>-enamine inhibitory intermediate similar to the intermediate seen in the <i>wt</i> SHV-1 structure. Taken together, our data reveals that the C2 side chain linker length and composition profoundly affect the formation of the <i>trans</i>-enamine intermediate of penam sulfones. We also show that the design of SA2-13 derivatives offers promise against IR SHV β-lactamases that possess the K234R substitution.</p></div>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Protein interactions", "protein structure", "protein synthesis", "Biomacromolecule-ligand interactions", "drug discovery", "Small molecules", "biophysics", "Protein folding", "microbiology", "Bacterial pathogens", "Gram negative", "proteomics", "crystallography", "Drugs and devices", "Drug research and development", "sulfones", "sa2-13", "c2"], "article_id"=>902671, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Elizabeth A. Rodkey", "Marisa L. Winkler", "Christopher R. Bethel", "Sundar Ram Reddy Pagadala", "John D. Buynak", "Robert A. Bonomo", "Focco van den Akker"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085892.s001", "https://dx.doi.org/10.1371/journal.pone.0085892.s002", "https://dx.doi.org/10.1371/journal.pone.0085892.s003"], "stats"=>{"downloads"=>2, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Penam_Sulfones_and_946_Lactamase_Inhibition_SA2_13_and_the_Importance_of_the_C2_Side_Chain_Length_and_Composition_/902671", "title"=>"Penam Sulfones and β-Lactamase Inhibition: SA2-13 and the Importance of the C2 Side Chain Length and Composition", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-01-16 03:25:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349508"], "description"=>"<p>Data collection and refinement statistics.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Protein interactions", "protein structure", "protein synthesis", "Biomacromolecule-ligand interactions", "drug discovery", "Small molecules", "biophysics", "Protein folding", "microbiology", "Bacterial pathogens", "Gram negative", "proteomics", "crystallography", "Drugs and devices", "Drug research and development", "refinement"], "article_id"=>902670, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Elizabeth A. Rodkey", "Marisa L. Winkler", "Christopher R. Bethel", "Sundar Ram Reddy Pagadala", "John D. Buynak", "Robert A. Bonomo", "Focco van den Akker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085892.t001", "stats"=>{"downloads"=>3, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Data_collection_and_refinement_statistics_/902670", "title"=>"Data collection and refinement statistics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-16 03:25:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349505"], "description"=>"<p>Temperature factors of protein atoms are represented by rainbow color-ramping from blue to red for temperature factors ranging from <5 to >40 Å<sup>2</sup>. Depicted are the structures of K234R SHV (A) and (B), wt SHV-1 (C) and (D), and R164S SHV (E) and (F). Uncomplexed structure are shown on the left (A), (C), and (E), whereas SA2-13 bound structures are on the right (B), (D), (F) with SA2-13 being depicted in grey ball-and-stick model. Completely disordered region not modeled in the SA2-13 bound R164S SHV structure is highlighted by red dashed oval.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Protein interactions", "protein structure", "protein synthesis", "Biomacromolecule-ligand interactions", "drug discovery", "Small molecules", "biophysics", "Protein folding", "microbiology", "Bacterial pathogens", "Gram negative", "proteomics", "crystallography", "Drugs and devices", "Drug research and development", "induced", "sa2-13"], "article_id"=>902667, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Elizabeth A. Rodkey", "Marisa L. Winkler", "Christopher R. Bethel", "Sundar Ram Reddy Pagadala", "John D. Buynak", "Robert A. Bonomo", "Focco van den Akker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085892.g008", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protein_disorder_induced_by_SA2_13_binding_/902667", "title"=>"Protein disorder induced by SA2-13 binding.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-16 03:25:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1349495"], "description"=>"<p>Synthesis of PSR-3-226, PSR-4-155, and PSR-4-157, the synthesis of SA2-13 is previously published <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085892#pone.0085892-Padayatti1\" target=\"_blank\">[10]</a>.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Protein interactions", "protein structure", "protein synthesis", "Biomacromolecule-ligand interactions", "drug discovery", "Small molecules", "biophysics", "Protein folding", "microbiology", "Bacterial pathogens", "Gram negative", "proteomics", "crystallography", "Drugs and devices", "Drug research and development", "synthesis", "sa2-13", "published"], "article_id"=>902657, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Elizabeth A. Rodkey", "Marisa L. Winkler", "Christopher R. Bethel", "Sundar Ram Reddy Pagadala", "John D. Buynak", "Robert A. Bonomo", "Focco van den Akker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085892.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Synthesis_of_PSR_3_226_PSR_4_155_and_PSR_4_157_the_synthesis_of_SA2_13_is_previously_published_10_/902657", "title"=>"Synthesis of PSR-3-226, PSR-4-155, and PSR-4-157, the synthesis of SA2-13 is previously published [10].", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-16 03:25:25"}

PMC Usage Stats | Further Information

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Relative Metric

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