Literature DB >> 23685211

Salmonella enterica MTAN at 1.36 Å resolution: a structure-based design of tailored transition state analogs.

Antti M Haapalainen1, Keisha Thomas, Peter C Tyler, Gary B Evans, Steven C Almo, Vern L Schramm.   

Abstract

Accumulation of 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH) in bacteria disrupts the S-adenosylmethionine pool to alter biological methylations, synthesis of polyamines, and production of quorum-sensing molecules. Bacterial metabolism of MTA and SAH depends on MTA/SAH nucleosidase (MTAN), an enzyme not present in humans and a target for quorum sensing because MTAN activity is essential for synthesis of autoinducer-2 molecules. Crystals of Salmonella enterica MTAN with product and transition state analogs of MTA and SAH explain the structural contacts causing pM binding affinity for the inhibitor and reveal a "water-wire" channel for the catalytic nucleophile. The crystal structure shows an extension of the binding pocket filled with polyethylene glycol. We exploited this discovery by the design and synthesis of tailored modifications of the currently existing transition state analogs to fill this site. This site was not anticipated in MTAN structures. Tailored inhibitors with dissociation constants of 5 to 15 pM are characterized.
Copyright © 2013 Elsevier Ltd. All rights reserved.

Entities:  

Mesh：

Substances：

Year:  2013        PMID： 23685211      PMCID： PMC3690532          DOI： 10.1016/j.str.2013.04.009

Source DB:  PubMed          Journal:  Structure        ISSN： 0969-2126            Impact factor:   5.006


  44 in total

1.  The enzymatic decomposition of S-adenosyl-L-methionine.

Authors:  S K SHAPIRO; A N MATHER
Journal:  J Biol Chem       Date:  1958-09       Impact factor: 5.157

2.  PRODRG: a tool for high-throughput crystallography of protein-ligand complexes.

Authors:  Alexander W Schüttelkopf; Daan M F van Aalten
Journal:  Acta Crystallogr D Biol Crystallogr       Date:  2004-07-21

3.  Picomolar inhibitors as transition-state probes of 5'-methylthioadenosine nucleosidases.

Authors:  Jemy A Gutierrez; Minkui Luo; Vipender Singh; Lei Li; Rosemary L Brown; Gillian E Norris; Gary B Evans; Richard H Furneaux; Peter C Tyler; Gavin F Painter; Dirk H Lenz; Vern L Schramm
Journal:  ACS Chem Biol       Date:  2007-11-20       Impact factor: 5.100

4.  Acyl homoserine-lactone quorum-sensing signal generation.

Authors:  M R Parsek; D L Val; B L Hanzelka; J E Cronan; E P Greenberg
Journal:  Proc Natl Acad Sci U S A       Date:  1999-04-13       Impact factor: 11.205

5.  Characterization of recombinant Eschericha coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase: analysis of enzymatic activity and substrate specificity.

Authors:  K A Cornell; W E Swarts; R D Barry; M K Riscoe
Journal:  Biochem Biophys Res Commun       Date:  1996-11-21       Impact factor: 3.575

Review 6.  Quorum sensing as an integral component of gene regulatory networks in Gram-negative bacteria.

Authors:  H Withers; S Swift; P Williams
Journal:  Curr Opin Microbiol       Date:  2001-04       Impact factor: 7.934

7.  Features and development of Coot.

Authors:  P Emsley; B Lohkamp; W G Scott; K Cowtan
Journal:  Acta Crystallogr D Biol Crystallogr       Date:  2010-03-24

8.  Targeting the polyamine pathway with transition-state analogue inhibitors of 5'-methylthioadenosine phosphorylase.

Authors:  Gary B Evans; Richard H Furneaux; Vern L Schramm; Vipender Singh; Peter C Tyler
Journal:  J Med Chem       Date:  2004-06-03       Impact factor: 7.446

Review 9.  Scaling and assessment of data quality.

Authors:  Philip Evans
Journal:  Acta Crystallogr D Biol Crystallogr       Date:  2005-12-14

10.  MolProbity: all-atom structure validation for macromolecular crystallography.

Authors:  Vincent B Chen; W Bryan Arendall; Jeffrey J Headd; Daniel A Keedy; Robert M Immormino; Gary J Kapral; Laura W Murray; Jane S Richardson; David C Richardson
Journal:  Acta Crystallogr D Biol Crystallogr       Date:  2009-12-21
View more
  10 in total

1.  Structural and biochemical characterization of Chlamydia trachomatis hypothetical protein CT263 supports that menaquinone synthesis occurs through the futalosine pathway.

Authors:  Michael L Barta; Keisha Thomas; Hongling Yuan; Scott Lovell; Kevin P Battaile; Vern L Schramm; P Scott Hefty
Journal:  J Biol Chem       Date:  2014-09-24       Impact factor: 5.157

2.  Transition State Structure and Inhibition of Rv0091, a 5'-Deoxyadenosine/5'-methylthioadenosine Nucleosidase from Mycobacterium tuberculosis.

Authors:  Hilda A Namanja-Magliano; Christopher F Stratton; Vern L Schramm
Journal:  ACS Chem Biol       Date:  2016-04-08       Impact factor: 5.100

3.  Transition State Analogue Inhibitors of 5'-Deoxyadenosine/5'-Methylthioadenosine Nucleosidase from Mycobacterium tuberculosis.

Authors:  Hilda A Namanja-Magliano; Gary B Evans; Rajesh K Harijan; Peter C Tyler; Vern L Schramm
Journal:  Biochemistry       Date:  2017-09-07       Impact factor: 3.162

4.  Selective Inhibitors of Helicobacter pylori Methylthioadenosine Nucleosidase and Human Methylthioadenosine Phosphorylase.

Authors:  Rajesh K Harijan; Oskar Hoff; Rodrigo G Ducati; Ross S Firestone; Brett M Hirsch; Gary B Evans; Vern L Schramm; Peter C Tyler
Journal:  J Med Chem       Date:  2019-03-28       Impact factor: 7.446

5.  Molecular dynamics study of the effect of active site protonation on Helicobacter pylori 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase.

Authors:  Mustafa Tekpinar; Ahmet Yildirim; Tsjerk A Wassenaar
Journal:  Eur Biophys J       Date:  2015-08-08       Impact factor: 1.733

6.  Transition-State Analogues of Campylobacter jejuni 5'-Methylthioadenosine Nucleosidase.

Authors:  Rodrigo G Ducati; Rajesh K Harijan; Scott A Cameron; Peter C Tyler; Gary B Evans; Vern L Schramm
Journal:  ACS Chem Biol       Date:  2018-10-19       Impact factor: 5.100

7.  Characterization of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidases from Borrelia burgdorferi: Antibiotic targets for Lyme disease.

Authors:  Kenneth A Cornell; Reece J Knippel; Gerald R Cortright; Meghan Fonken; Christian Guerrero; Amy R Hall; Kristen A Mitchell; John H Thurston; Patrick Erstad; Aoxiang Tao; Dong Xu; Nikhat Parveen
Journal:  Biochim Biophys Acta Gen Subj       Date:  2019-10-31       Impact factor: 3.770

8.  New Antibiotic Candidates against Helicobacter pylori.

Authors:  Shanzhi Wang; Scott A Cameron; Keith Clinch; Gary B Evans; Zhimeng Wu; Vern L Schramm; Peter C Tyler
Journal:  J Am Chem Soc       Date:  2015-11-09       Impact factor: 15.419

9.  Catalytic site cooperativity in dimeric methylthioadenosine nucleosidase.

Authors:  Shanzhi Wang; Keisha Thomas; Vern L Schramm
Journal:  Biochemistry       Date:  2014-02-21       Impact factor: 3.162

Review 10.  Interference With Quorum-Sensing Signal Biosynthesis as a Promising Therapeutic Strategy Against Multidrug-Resistant Pathogens.

Authors:  Osmel Fleitas Martínez; Pietra Orlandi Rigueiras; Állan da Silva Pires; William Farias Porto; Osmar Nascimento Silva; Cesar de la Fuente-Nunez; Octavio Luiz Franco
Journal:  Front Cell Infect Microbiol       Date:  2019-02-05       Impact factor: 5.293
  10 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.