Acta crystallographica. Section F, Structural biology communications最新文献

{"title":"Structural basis for the development of potential inhibitors targeting FadD23 from Mycobacterium tuberculosis","authors":"Mengrong Yan,&nbsp;Mengyuan Ma,&nbsp;Rong Chen,&nbsp;Yangzi Cao,&nbsp;Wei Zhang,&nbsp;Xiang Liu","doi":"10.1107/S2053230X23005836","DOIUrl":"10.1107/S2053230X23005836","url":null,"abstract":"<p>Sulfolipid-1 (SL-1) is a lipid that is abundantly found in the cell wall of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>). <i>Mtb</i>FadD23 is crucial in the SL-1 synthesis pathway. Previously, 5′-<i>O</i>-[<i>N</i>-(11-phenoxyundecanoyl)sulfamoyl]adenosine (PhU-AMS) has been shown to be a general inhibitor of fatty-acid-adenylating enzymes (FadDs) in <i>Mtb</i>. However, the fatty acyl-AMP ligase (FAAL) class of FadDs, which includes <i>Mtb</i>FadD23, appears to be functionally nonredundant in the production of multiple fatty acids. In this study, the ability of PhU-AMS to bind to <i>Mtb</i>FadD23 was examined under <i>in vitro</i> conditions. The crystal structure of the <i>Mtb</i>FadD23–PhU-AMS complex was determined at a resolution of 2.64 Å. Novel features were identified by structural analysis and comparison. Although PhU-AMS could bind to <i>Mtb</i>FadD23, it did not inhibit the FAAL adenylation activity of <i>Mtb</i>FadD23. However, PhU-AMS improved the main <i>T</i>_m value in a differential scanning fluorimetry assay, and a structural comparison of <i>Mtb</i>FadD23–PhU-AMS with FadD32 and PA1221 suggested that PhU-AMS blocks the loading of the acyl chain onto Pks2. This study sheds light on the structure-based design of specific inhibitors of <i>Mtb</i>FadD23 and general inhibitors of FAALs.</p>","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1107/S2053230X23005836","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10040082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure of a superoxide dismutase from a tardigrade: Ramazzottius varieornatus strain YOKOZUNA-1","authors":"Kee-Shin Sim,&nbsp;Tsuyoshi Inoue","doi":"10.1107/S2053230X2300523X","DOIUrl":"10.1107/S2053230X2300523X","url":null,"abstract":"<p>Superoxide dismutase (SOD) is an essential and ubiquitous antioxidant protein that is widely present in biological systems. The anhydrobiotic tardigrades are some of the toughest micro-animals. They have an expanded set of genes for antioxidant proteins such as SODs. These proteins are thought to play an essential role in oxidative stress resistance in critical situations such as desiccation, although their functions at the molecular level have yet to be explored. Here, crystal structures of a copper/zinc-containing SOD (<i>Rv</i>SOD15) from an anhydrobiotic tardigrade, <i>Ramazzottius varieornatus</i> strain YOKOZUNA-1, are reported. In <i>Rv</i>SOD15, one of the histidine ligands of the catalytic copper center is replaced by a valine (Val87). The crystal structures of the wild type and the V87H mutant show that even though a histidine is placed at position 87, a nearby flexible loop can destabilize the coordination of His87 to the Cu atom. Model structures of other <i>Rv</i>SODs were investigated and it was found that some of them are also unusual SODs, with features such as deletion of the electrostatic loop or β3 sheet and unusual metal-binding residues. These studies show that <i>Rv</i>SOD15 and some other <i>Rv</i>SODs may have evolved to lose the SOD function, suggesting that gene duplications of antioxidant proteins do not solely explain the high stress tolerance of anhydrobiotic tardigrades.</p>","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1107/S2053230X2300523X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9790666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tetracycline-modifying enzyme SmTetX from Stenotrophomonas maltophilia","authors":"Martin Malý,&nbsp;Petr Kolenko,&nbsp;Jan Stránský,&nbsp;Leona Švecová,&nbsp;Jarmila Dušková,&nbsp;Tomáš Koval',&nbsp;Tereza Skálová,&nbsp;Mária Trundová,&nbsp;Kristýna Adámková,&nbsp;Jiří Černý,&nbsp;Paulína Božíková,&nbsp;Jan Dohnálek","doi":"10.1107/S2053230X23005381","DOIUrl":"10.1107/S2053230X23005381","url":null,"abstract":"<p>The resistance of the emerging human pathogen <i>Stenotrophomonas maltophilia</i> to tetracycline antibiotics mainly depends on multidrug efflux pumps and ribosomal protection enzymes. However, the genomes of several strains of this Gram-negative bacterium code for a FAD-dependent monooxygenase (<i>Sm</i>TetX) homologous to tetracycline destructases. This protein was recombinantly produced and its structure and function were investigated. Activity assays using <i>Sm</i>TetX showed its ability to modify oxytetracycline with a catalytic rate comparable to those of other destructases. <i>Sm</i>TetX shares its fold with the tetracycline destructase TetX from <i>Bacteroides thetaiotaomicron</i>; however, its active site possesses an aromatic region that is unique in this enzyme family. A docking study confirmed tetracycline and its analogues to be the preferred binders amongst various classes of antibiotics.</p>","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1107/S2053230X23005381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal structure of CmnB involved in the biosynthesis of the nonproteinogenic amino acid l-2,3-diaminopropionic acid","authors":"Shu-Ing Toh,&nbsp;Chieh-Ling Lo,&nbsp;Chin-Yuan Chang","doi":"10.1107/S2053230X23005769","DOIUrl":"10.1107/S2053230X23005769","url":null,"abstract":"<p><span>l</span>-2,3-Diaminopropionic acid (<span>l</span>-Dap) is a nonproteinogenic amino acid that plays as an important role as a building block in the biosynthesis of several natural products, including capreomycin, viomycin, zwittermicin, staphyloferrin and dapdiamide. A previous study reported that CmnB and CmnK are two enzymes that are involved in the formation of <span>l</span>-Dap in the biosynthesis of capreomycin. CmnB catalyzes the condensation reaction of <i>O</i>-phospho-<span>l</span>-serine and <span>l</span>-glutamic acid to generate <i>N</i>-(1-amino-1-carboxyl-2-ethyl)glutamic acid, which subsequently undergoes oxidative hydrolysis via CmnK to generate the product <span>l</span>-Dap. Here, the crystal structure of CmnB in complex with the reaction intermediate PLP-α-aminoacrylate is reported at 2.2 Å resolution. Notably, CmnB is the second known example of a PLP-dependent enzyme that forms a monomeric structure in crystal packing. The crystal structure of CmnB also provides insights into the catalytic mechanism of the enzyme and supports the biosynthetic pathway of <span>l</span>-Dap reported in previous studies.</p>","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1107/S2053230X23005769","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9858337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AlphaFold and the future of structural biology","authors":"Randy J. Read,&nbsp;Edward N. Baker,&nbsp;Charles S. Bond,&nbsp;Elspeth F. Garman,&nbsp;Mark J. van Raaij","doi":"10.1107/S2053230X23004934","DOIUrl":"10.1107/S2053230X23004934","url":null,"abstract":"<p>This editorial acknowledges the transformative impact of new machine-learning methods, such as the use of AlphaFold, but also makes the case for the continuing need for experimental structural biology.</p>","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327576/pdf/f-79-00166.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial structural genomics target enabled by a recently discovered potent fungal acetyl-CoA synthetase inhibitor","authors":"Nicholas D. DeBouver,&nbsp;Madison J. Bolejack,&nbsp;Taiwo E. Esan,&nbsp;Damian J. Krysan,&nbsp;Timothy J. Hagen,&nbsp;Jan Abendroth","doi":"10.1107/S2053230X23003801","DOIUrl":"10.1107/S2053230X23003801","url":null,"abstract":"<p>The compound ethyl-adenosyl monophosphate ester (ethyl-AMP) has been shown to effectively inhibit acetyl-CoA synthetase (ACS) enzymes and to facilitate the crystallization of fungal ACS enzymes in various contexts. In this study, the addition of ethyl-AMP to a bacterial ACS from <i>Legionella pneumophila</i> resulted in the determination of a co-crystal structure of this previously elusive structural genomics target. The dual functionality of ethyl-AMP in both inhibiting ACS enzymes and promoting crystallization establishes its significance as a valuable resource for advancing structural investigations of this class of proteins.</p>","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1107/S2053230X23003801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9613663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal structure of thermostable acetaldehyde dehydrogenase from the hyperthermophilic archaeon Sulfolobus tokodaii","authors":"Shohei Mine,&nbsp;Makoto Nakabayashi,&nbsp;Kazuhiko Ishikawa","doi":"10.1107/S2053230X23004430","DOIUrl":"10.1107/S2053230X23004430","url":null,"abstract":"<p>Aldehyde dehydrogenase (ALDH) is widely distributed in nature and its characteristics have been examined. ALDH plays an important role in aldehyde detoxification. Sources of aldehydes include incomplete combustion and emissions from paints, linoleum and varnishes in the living environment. Acetaldehyde is also considered to be carcinogenic and toxic. Thermostable ALDH from the hyperthermophilic archaeon <i>Sulfolobus tokodaii</i> exhibits high activity towards acetaldehyde and has potential applications as a biosensor for acetaldehyde. Thermostable ALDH displays a unique and wide adaptability. Therefore, its crystal structure can provide new insights into the catalytic mechanism and potential applications of ALDHs. However, a crystal structure of a thermostable ALDH exhibiting high activity towards acetaldehyde has not been reported to date. In this study, crystals of recombinant thermostable ALDH from <i>S. tokodaii</i> were prepared and the crystal structure of its holo form was determined. A crystal of the enzyme was prepared and its structure in complex with NADP was determined at a resolution of 2.2 Å. This structural analysis may facilitate further studies on catalytic mechanisms and applications.</p>","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1107/S2053230X23004430","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9552329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal structure of a putative 3-hydroxypimelyl-CoA dehydrogenase, Hcd1, from Syntrophus aciditrophicus strain SB at 1.78 Å resolution","authors":"David M. Dinh,&nbsp;Leonard M. Thomas,&nbsp;Elizabeth A. Karr","doi":"10.1107/S2053230X23004399","DOIUrl":"10.1107/S2053230X23004399","url":null,"abstract":"<p><i>Syntrophus aciditrophicus</i> strain SB is a model syntroph that degrades benzoate and alicyclic acids. The structure of a putative 3-hydroxypimelyl-CoA dehydrogenase from <i>S. aciditrophicus</i> strain SB (<i>Sa</i>Hcd1) was resolved at 1.78 Å resolution. <i>Sa</i>Hcd1 contains sequence motifs and structural features that belong to the short-chain dehydrogenase/reductase (SDR) family of NADPH-dependent oxidoreductases. <i>Sa</i>Hcd1 is proposed to concomitantly reduce NAD⁺ or NADP⁺ to NADH or NADPH, respectively, while converting 3-hydroxypimelyl-CoA to 3-oxopimeyl-CoA. Further enzymatic studies are needed to confirm the function of <i>Sa</i>Hcd1.</p>","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1107/S2053230X23004399","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9707320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal structure of a three-tetrad, parallel, K+-stabilized human telomeric G-quadruplex at 1.35 Å resolution","authors":"E. V. Chen,&nbsp;J. M. Nicoludis,&nbsp;B. M. Powell,&nbsp;K. S. Li,&nbsp;L. A. Yatsunyk","doi":"10.1107/S2053230X23003977","DOIUrl":"https://doi.org/10.1107/S2053230X23003977","url":null,"abstract":"<p>The crystal structure of the G-rich human telomeric DNA Tel22 has been determined at 1.35 Å resolution in space group <i>P</i>6. Tel22 forms a non-canonical DNA structure called the G-quadruplex. The space group and unit-cell parameters are comparable to those in the crystal structures with PDB codes 6ip3 (1.40 Å resolution) and 1kf1 (2.15 Å resolution). The G-quadruplexes are highly similar in all of the structures. However, this structure of Tel22 displays clear density for polyethylene glycol and two potassium ions, which are located outside the ion channel in the G-quadruplex and play an important role in stabilizing the crystal contacts. In addition, 111 water molecules were identified (compared with 79 and 68 in PDB entries 6ip3 and 1kf1, respectively) that participate in intricate and extensive networks providing high stability to the G-quadruplex.</p>","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50154302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The catalytic domains of Streptococcus mutans glucosyltransferases: a structural analysis","authors":"Norbert Schormann,&nbsp;Manisha Patel,&nbsp;Luke Thannickal,&nbsp;Sangeetha Purushotham,&nbsp;Ren Wu,&nbsp;Joshua L. Mieher,&nbsp;Hui Wu,&nbsp;Champion Deivanayagam","doi":"10.1107/S2053230X23003199","DOIUrl":"10.1107/S2053230X23003199","url":null,"abstract":"<p><i>Streptococcus mutans</i>, found in the human oral cavity, is a significant contributor to the pathogenesis of dental caries. This bacterium expresses three genetically distinct types of glucosyltransferases named GtfB (GTF-I), GtfC (GTF-SI) and GtfD (GTF-S) that play critical roles in the development of dental plaque. The catalytic domains of GtfB, GtfC and GtfD contain conserved active-site residues for the overall enzymatic activity that relate to hydrolytic glycosidic cleavage of sucrose to glucose and fructose, release of fructose and generation of a glycosyl-enzyme intermediate in the reducing end. In a subsequent transglycosylation step, the glucosyl moiety is transferred to the nonreducing end of an acceptor to form a growing glucan polymer chain made up of glucose molecules. It has been proposed that both sucrose breakdown and glucan synthesis occur in the same active site of the catalytic domain, although the active site does not appear to be large enough to accommodate both functions. These three enzymes belong to glycoside hydrolase family 70 (GH70), which shows homology to glycoside hydrolase family 13 (GH13). GtfC synthesizes both soluble and insoluble glucans (α-1,3 and α-1,6 glycosidic linkages), while GtfB and GtfD synthesize only insoluble or soluble glucans, respectively. Here, crystal structures of the catalytic domains of GtfB and GtfD are reported. These structures are compared with previously determined structures of the catalytic domain of GtfC. With this work, apo structures and inhibitor-complex structures with acarbose are now available for the catalytic domains of GtfC and GtfB. The structure of GtfC with maltose allows further identification and comparison of active-site residues. A model of sucrose binding to GtfB is also included. The new structure of the catalytic domain of GtfD affords a structural comparison of the three <i>S. mutans</i> glycosyltransferases. Unfortunately, the catalytic domain of GtfD is not complete since crystallization resulted in the structure of a truncated protein lacking approximately 200 N-terminal residues of domain IV.</p>","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1107/S2053230X23003199","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9442517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}