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Larissa Podust

TitleAssociate Professor In Residence
InstitutionUniversity of California San Diego
DepartmentSchool of Pharmacy and Pharmaceutical Science
Address9500 Gilman Drive #0755
La Jolla CA 92093
Phone858-822-2548
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    Collapse Research 
    Collapse Research Activities and Funding
    Brain Penetrant Microtubule-Stabilizers to treat CNS-invasive parasitic diseases
    NIH/NIAID R21AI133394Jun 1, 2018 - May 31, 2020
    Role: Co-Principal Investigator
    Protein-Protein Interaction in Natural Product Biosynthesis
    NIH/NIGMS R01GM095970Mar 1, 2012 - Jan 31, 2020
    Role: Principal Investigator
    Structure-Aided Design of CYP51 Inhibitors for Treatment of Parasitic Infections
    NIH/NIAID R01AI095437Jun 20, 2011 - May 31, 2016
    Role: Principal Investigator
    Structure and Engineering of Natural Product Cyctochrome P450 Enzymes
    NIH/NIGMS R01GM078553May 15, 2007 - Jan 31, 2016
    Role: Principal Investigator

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Debnath A, Calvet CM, Jennings G, Zhou W, Aksenov A, Luth MR, Abagyan R, Nes WD, McKerrow JH, Podust L. CYP51 is an essential drug target for the treatment of primary amoebic meningoencephalitis (PAM). PLoS Negl Trop Dis. 2017 12; 11(12):e0006104. PMID: 29284029.
      View in: PubMed
    2. Calvet CM, Choi JY, Thomas D, Suzuki B, Hirata K, Lostracco-Johnson S, de Mesquita LB, Nogueira A, Meuser-Batista M, Silva TA, Siqueira-Neto JL, Roush WR, de Souza Pereira MC, McKerrow JH, Podust L. 4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection. PLoS Negl Trop Dis. 2017 12; 11(12):e0006132. PMID: 29281643.
      View in: PubMed
    3. Long T, Rojo-Arreola L, Shi D, El-Sakkary N, Jarnagin K, Rock F, Meewan M, Rascón AA, Lin L, Cunningham KA, Lemieux GA, Podust L, Abagyan R, Ashrafi K, McKerrow JH, Caffrey CR. Phenotypic, chemical and functional characterization of cyclic nucleotide phosphodiesterase 4 (PDE4) as a potential anthelmintic drug target. PLoS Negl Trop Dis. 2017 Jul; 11(7):e0005680. PMID: 28704396.
      View in: PubMed
    4. Tietz DR, Podust L, Sherman DH, Pochapsky TC. Solution Conformations and Dynamics of Substrate-Bound Cytochrome P450 MycG. Biochemistry. 2017 05 30; 56(21):2701-2714. PMID: 28488849.
      View in: PubMed
    5. Ottilie S, Goldgof GM, Calvet CM, Jennings GK, LaMonte G, Schenken J, Vigil E, Kumar P, McCall LI, Lopes ES, Gunawan F, Yang J, Suzuki Y, Siqueira-Neto JL, McKerrow JH, Amaro RE, Podust L, Durrant JD, Winzeler EA. Rapid Chagas Disease Drug Target Discovery Using Directed Evolution in Drug-Sensitive Yeast. ACS Chem Biol. 2017 Feb 17; 12(2):422-434. PMID: 27977118.
      View in: PubMed
    6. DeMars MD, Sheng F, Park SR, Lowell AN, Podust L, Sherman DH. Biochemical and Structural Characterization of MycCI, a Versatile P450 Biocatalyst from the Mycinamicin Biosynthetic Pathway. ACS Chem Biol. 2016 09 16; 11(9):2642-54. PMID: 27420774; PMCID: PMC5026600 [Available on 09/16/17].
    7. Parsonage D, Sheng F, Hirata K, Debnath A, McKerrow JH, Reed SL, Abagyan R, Poole LB, Podust L. X-ray structures of thioredoxin and thioredoxin reductase from Entamoeba histolytica and prevailing hypothesis of the mechanism of Auranofin action. J Struct Biol. 2016 May; 194(2):180-90. PMID: 26876147; PMCID: PMC5003402 [Available on 05/01/17].
    8. Ziniel PD, Karumudi B, Barnard AH, Fisher EM, Thatcher GR, Podust L, Williams DL. Correction: The Schistosoma mansoni Cytochrome P450 (CYP3050A1) Is Essential for Worm Survival and Egg Development. PLoS Negl Trop Dis. 2016 Feb; 10(2):e0004439. PMID: 26828364; PMCID: PMC4734659.
    9. Ziniel PD, Karumudi B, Barnard AH, Fisher EM, Thatcher GR, Podust L, Williams DL. The Schistosoma mansoni Cytochrome P450 (CYP3050A1) Is Essential for Worm Survival and Egg Development. PLoS Negl Trop Dis. 2015 Dec; 9(12):e0004279. PMID: 26713732; PMCID: PMC4694641.
    10. Narayan AR, Jiménez-Osés G, Liu P, Negretti S, Zhao W, Gilbert MM, Ramabhadran RO, Yang YF, Furan LR, Li Z, Podust L, Montgomery J, Houk KN, Sherman DH. Enzymatic hydroxylation of an unactivated methylene C-H bond guided by molecular dynamics simulations. Nat Chem. 2015 Aug; 7(8):653-60. PMID: 26201742; PMCID: PMC4518477.
    11. McCall LI, El Aroussi A, Choi JY, Vieira DF, De Muylder G, Johnston JB, Chen S, Kellar D, Siqueira-Neto JL, Roush WR, Podust L, McKerrow JH. Targeting Ergosterol biosynthesis in Leishmania donovani: essentiality of sterol 14 alpha-demethylase. PLoS Negl Trop Dis. 2015 Mar; 9(3):e0003588. PMID: 25768284; PMCID: PMC4359151.
    12. Vieira DF, Choi JY, Calvet CM, Siqueira-Neto JL, Johnston JB, Kellar D, Gut J, Cameron MD, McKerrow JH, Roush WR, Podust L. Binding mode and potency of N-indolyloxopyridinyl-4-aminopropanyl-based inhibitors targeting Trypanosoma cruzi CYP51. J Med Chem. 2014 Dec 11; 57(23):10162-75. PMID: 25393646; PMCID: PMC4266343.
    13. Choi JY, Podust L, Roush WR. Drug strategies targeting CYP51 in neglected tropical diseases. Chem Rev. 2014 Nov 26; 114(22):11242-71. PMID: 25337991; PMCID: PMC4254036.
    14. Calvet CM, Vieira DF, Choi JY, Kellar D, Cameron MD, Siqueira-Neto JL, Gut J, Johnston JB, Lin L, Khan S, McKerrow JH, Roush WR, Podust L. 4-Aminopyridyl-based CYP51 inhibitors as anti-Trypanosoma cruzi drug leads with improved pharmacokinetic profile and in vivo potency. J Med Chem. 2014 Aug 28; 57(16):6989-7005. PMID: 25101801; PMCID: PMC4148169.
    15. Vieira DF, Choi JY, Roush WR, Podust L. Expanding the binding envelope of CYP51 inhibitors targeting Trypanosoma cruzi with 4-aminopyridyl-based sulfonamide derivatives. Chembiochem. 2014 May 26; 15(8):1111-20. PMID: 24771705; PMCID: PMC4091728.
    16. Negretti S, Narayan AR, Chiou KC, Kells PM, Stachowski JL, Hansen DA, Podust L, Montgomery J, Sherman DH. Directing group-controlled regioselectivity in an enzymatic C-H bond oxygenation. J Am Chem Soc. 2014 Apr 02; 136(13):4901-4. PMID: 24627965; PMCID: PMC4012894.
    17. Zhang W, Liu Y, Yan J, Cao S, Bai F, Yang Y, Huang S, Yao L, Anzai Y, Kato F, Podust L, Sherman DH, Li S. New reactions and products resulting from alternative interactions between the P450 enzyme and redox partners. J Am Chem Soc. 2014 Mar 05; 136(9):3640-6. PMID: 24521145; PMCID: PMC3985502.
    18. Choi JY, Calvet CM, Vieira DF, Gunatilleke SS, Cameron MD, McKerrow JH, Podust L, Roush WR. R-Configuration of 4-Aminopyridyl-Based Inhibitors of CYP51 Confers Superior Efficacy Against Trypanosoma cruzi. ACS Med Chem Lett. 2014 Apr 10; 5(4):434-9. PMID: 24900854; PMCID: PMC4027616.
    19. Choi JY, Calvet CM, Gunatilleke SS, Ruiz C, Cameron MD, McKerrow JH, Podust L, Roush WR. Rational development of 4-aminopyridyl-based inhibitors targeting Trypanosoma cruzi CYP51 as anti-chagas agents. J Med Chem. 2013 Oct 10; 56(19):7651-68. PMID: 24079662; PMCID: PMC3864028.
    20. García-Fernández E, Frank DJ, Galán B, Kells PM, Podust L, García JL, Ortiz de Montellano PR. A highly conserved mycobacterial cholesterol catabolic pathway. Environ Microbiol. 2013 Aug; 15(8):2342-59. PMID: 23489718; PMCID: PMC3706556.
    21. Choy JW, Bryant C, Calvet CM, Doyle PS, Gunatilleke SS, Leung SS, Ang KK, Chen S, Gut J, Oses-Prieto JA, Johnston JB, Arkin MR, Burlingame AL, Taunton J, Jacobson MP, McKerrow JM, Podust L, Renslo AR. Chemical-biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target. Beilstein J Org Chem. 2013; 9:15-25. PMID: 23400640; PMCID: PMC3566858.
    22. Li S, Tietz DR, Rutaganira FU, Kells PM, Anzai Y, Kato F, Pochapsky TC, Sherman DH, Podust L. Substrate recognition by the multifunctional cytochrome P450 MycG in mycinamicin hydroxylation and epoxidation reactions. J Biol Chem. 2012 Nov 02; 287(45):37880-90. PMID: 22952225; PMCID: PMC3488060.
    23. Gunatilleke SS, Calvet CM, Johnston JB, Chen CK, Erenburg G, Gut J, Engel JC, Ang KK, Mulvaney J, Chen S, Arkin MR, McKerrow JH, Podust L. Diverse inhibitor chemotypes targeting Trypanosoma cruzi CYP51. PLoS Negl Trop Dis. 2012; 6(7):e1736. PMID: 22860142; PMCID: PMC3409115.
    24. Podust L, Sherman DH. Diversity of P450 enzymes in the biosynthesis of natural products. Nat Prod Rep. 2012 Oct; 29(10):1251-66. PMID: 22820933; PMCID: PMC3454455.
    25. Carlson JC, Li S, Gunatilleke SS, Anzai Y, Burr DA, Podust L, Sherman DH. Tirandamycin biosynthesis is mediated by co-dependent oxidative enzymes. Nat Chem. 2011 Jul 17; 3(8):628-33. PMID: 21778983; PMCID: PMC3154026.
    26. Ouellet H, Kells PM, Ortiz de Montellano PR, Podust L. Reverse type I inhibitor of Mycobacterium tuberculosis CYP125A1. Bioorg Med Chem Lett. 2011 Jan 01; 21(1):332-7. PMID: 21109436; PMCID: PMC3011832.
    27. Kells PM, Ouellet H, Santos-Aberturas J, Aparicio JF, Podust L. Structure of cytochrome P450 PimD suggests epoxidation of the polyene macrolide pimaricin occurs via a hydroperoxoferric intermediate. Chem Biol. 2010 Aug 27; 17(8):841-51. PMID: 20797613; PMCID: PMC2932657.
    28. Ivanov AS, Gnedenko OV, Molnar AA, Archakov AI, Podust L. FMN binding site of yeast NADPH-cytochrome P450 reductase exposed at the surface is highly specific. ACS Chem Biol. 2010 Aug 20; 5(8):767-76. PMID: 20557022; PMCID: PMC2924936.
    29. Johnston JB, Ouellet H, Podust L, Ortiz de Montellano PR. Structural control of cytochrome P450-catalyzed ?-hydroxylation. Arch Biochem Biophys. 2011 Mar 01; 507(1):86-94. PMID: 20727847; PMCID: PMC2997901.
    30. Ouellet H, Guan S, Johnston JB, Chow ED, Kells PM, Burlingame AL, Cox JS, Podust L, de Montellano PR. Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest-4-en-3-one. Mol Microbiol. 2010 Aug; 77(3):730-42. PMID: 20545858; PMCID: PMC2909382.
    31. Doyle PS, Chen CK, Johnston JB, Hopkins SD, Leung SS, Jacobson MP, Engel JC, McKerrow JH, Podust L. A nonazole CYP51 inhibitor cures Chagas' disease in a mouse model of acute infection. Antimicrob Agents Chemother. 2010 Jun; 54(6):2480-8. PMID: 20385875; PMCID: PMC2876414.
    32. Chen CK, Leung SS, Guilbert C, Jacobson MP, McKerrow JH, Podust L. Structural characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei bound to the antifungal drugs posaconazole and fluconazole. PLoS Negl Trop Dis. 2010 Apr 06; 4(4):e651. PMID: 20386598; PMCID: PMC2850312.
    33. von Kries JP, Warrier T, Podust L. Identification of small-molecule scaffolds for p450 inhibitors. Curr Protoc Microbiol. 2010 Feb; Chapter 17:Unit17.4. PMID: 20131225.
      View in: PubMed
    34. Johnston JB, Kells PM, Podust L, Ortiz de Montellano PR. Biochemical and structural characterization of CYP124: a methyl-branched lipid omega-hydroxylase from Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2009 Dec 08; 106(49):20687-92. PMID: 19933331.
      View in: PubMed
    35. Li S, Chaulagain MR, Knauff AR, Podust L, Montgomery J, Sherman DH. Selective oxidation of carbolide C-H bonds by an engineered macrolide P450 mono-oxygenase. Proc Natl Acad Sci U S A. 2009 Nov 03; 106(44):18463-8. PMID: 19833867; PMCID: PMC2774028.
    36. Podust L, Ouellet H, von Kries JP, de Montellano PR. Interaction of Mycobacterium tuberculosis CYP130 with heterocyclic arylamines. J Biol Chem. 2009 Sep 11; 284(37):25211-9. PMID: 19605350; PMCID: PMC2757224.
    37. McKerrow JH, Doyle PS, Engel JC, Podust L, Robertson SA, Ferreira R, Saxton T, Arkin M, Kerr ID, Brinen LS, Craik CS. Two approaches to discovering and developing new drugs for Chagas disease. Mem Inst Oswaldo Cruz. 2009 Jul; 104 Suppl 1:263-9. PMID: 19753483; PMCID: PMC4156466.
    38. Chen CK, Doyle PS, Yermalitskaya LV, Mackey ZB, Ang KK, McKerrow JH, Podust L. Trypanosoma cruzi CYP51 inhibitor derived from a Mycobacterium tuberculosis screen hit. PLoS Negl Trop Dis. 2009; 3(2):e372. PMID: 19190730; PMCID: PMC2629123.
    39. Li S, Ouellet H, Sherman DH, Podust L. Analysis of transient and catalytic desosamine-binding pockets in cytochrome P-450 PikC from Streptomyces venezuelae. J Biol Chem. 2009 Feb 27; 284(9):5723-30. PMID: 19124459; PMCID: PMC2931524.
    40. Podust L, Ioanoviciu A, Ortiz de Montellano PR. 2.3 A X-ray structure of the heme-bound GAF domain of sensory histidine kinase DosT of Mycobacterium tuberculosis. Biochemistry. 2008 Nov 25; 47(47):12523-31. PMID: 18980385; PMCID: PMC2645934.
    41. Eddine AN, von Kries JP, Podust MV, Warrier T, Kaufmann SH, Podust L. X-ray structure of 4,4'-dihydroxybenzophenone mimicking sterol substrate in the active site of sterol 14alpha-demethylase (CYP51). J Biol Chem. 2008 May 30; 283(22):15152-9. PMID: 18367444; PMCID: PMC2397474.
    42. Ouellet H, Podust L, de Montellano PR. Mycobacterium tuberculosis CYP130: crystal structure, biophysical characterization, and interactions with antifungal azole drugs. J Biol Chem. 2008 Feb 22; 283(8):5069-80. PMID: 18089574; PMCID: PMC2958778.
    43. Li S, Podust L, Sherman DH. Engineering and analysis of a self-sufficient biosynthetic cytochrome P450 PikC fused to the RhFRED reductase domain. J Am Chem Soc. 2007 Oct 31; 129(43):12940-1. PMID: 17915876; PMCID: PMC2572779.
    44. Podust L, von Kries JP, Eddine AN, Kim Y, Yermalitskaya LV, Kuehne R, Ouellet H, Warrier T, Alteköster M, Lee JS, Rademann J, Oschkinat H, Kaufmann SH, Waterman MR. Small-molecule scaffolds for CYP51 inhibitors identified by high-throughput screening and defined by X-ray crystallography. Antimicrob Agents Chemother. 2007 Nov; 51(11):3915-23. PMID: 17846131; PMCID: PMC2151439.
    45. Sherman DH, Li S, Yermalitskaya LV, Kim Y, Smith JA, Waterman MR, Podust L. The structural basis for substrate anchoring, active site selectivity, and product formation by P450 PikC from Streptomyces venezuelae. J Biol Chem. 2006 Sep 08; 281(36):26289-97. PMID: 16825192; PMCID: PMC2939096.
    46. Zhao B, Waterman MR, Isin EM, Sundaramoorthy M, Podust L. Ligand-assisted inhibition in cytochrome P450 158A2 from Streptomyces coelicolor A3(2). Biochemistry. 2006 Jun 20; 45(24):7493-500. PMID: 16768445.
      View in: PubMed
    47. Lamb DC, Kim Y, Yermalitskaya LV, Yermalitsky VN, Lepesheva GI, Kelly SL, Waterman MR, Podust L. A second FMN binding site in yeast NADPH-cytochrome P450 reductase suggests a mechanism of electron transfer by diflavin reductases. Structure. 2006 Jan; 14(1):51-61. PMID: 16407065.
      View in: PubMed
    48. Wu ZL, Podust L, Guengerich FP. Expansion of substrate specificity of cytochrome P450 2A6 by random and site-directed mutagenesis. J Biol Chem. 2005 Dec 09; 280(49):41090-100. PMID: 16215230.
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    49. Zhao B, Guengerich FP, Bellamine A, Lamb DC, Izumikawa M, Lei L, Podust L, Sundaramoorthy M, Kalaitzis JA, Reddy LM, Kelly SL, Moore BS, Stec D, Voehler M, Falck JR, Shimada T, Waterman MR. Binding of two flaviolin substrate molecules, oxidative coupling, and crystal structure of Streptomyces coelicolor A3(2) cytochrome P450 158A2. J Biol Chem. 2005 Mar 25; 280(12):11599-607. PMID: 15659395.
      View in: PubMed
    50. Podust L, Yermalitskaya LV, Lepesheva GI, Podust VN, Dalmasso EA, Waterman MR. Estriol bound and ligand-free structures of sterol 14alpha-demethylase. Structure. 2004 Nov; 12(11):1937-45. PMID: 15530358.
      View in: PubMed
    51. Podust L, Bach H, Kim Y, Lamb DC, Arase M, Sherman DH, Kelly SL, Waterman MR. Comparison of the 1.85 A structure of CYP154A1 from Streptomyces coelicolor A3(2) with the closely related CYP154C1 and CYPs from antibiotic biosynthetic pathways. Protein Sci. 2004 Jan; 13(1):255-68. PMID: 14691240; PMCID: PMC2286509.
    52. Tirona RG, Leake BF, Podust L, Kim RB. Identification of amino acids in rat pregnane X receptor that determine species-specific activation. Mol Pharmacol. 2004 Jan; 65(1):36-44. PMID: 14722235.
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    53. Podust L, Kim Y, Arase M, Neely BA, Beck BJ, Bach H, Sherman DH, Lamb DC, Kelly SL, Waterman MR. The 1.92-A structure of Streptomyces coelicolor A3(2) CYP154C1. A new monooxygenase that functionalizes macrolide ring systems. J Biol Chem. 2003 Apr 04; 278(14):12214-21. PMID: 12519772.
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    54. Lamb DC, Fowler K, Kieser T, Manning N, Podust L, Waterman MR, Kelly DE, Kelly SL. Sterol 14alpha-demethylase activity in Streptomyces coelicolor A3(2) is associated with an unusual member of the CYP51 gene family. Biochem J. 2002 Jun 01; 364(Pt 2):555-62. PMID: 12023899; PMCID: PMC1222601.
    55. Lamb DC, Skaug T, Song HL, Jackson CJ, Podust L, Waterman MR, Kell DB, Kelly DE, Kelly SL. The cytochrome P450 complement (CYPome) of Streptomyces coelicolor A3(2). J Biol Chem. 2002 Jul 05; 277(27):24000-5. PMID: 11943767.
      View in: PubMed
    56. Podust L, Stojan J, Poulos TL, Waterman MR. Substrate recognition sites in 14alpha-sterol demethylase from comparative analysis of amino acid sequences and X-ray structure of Mycobacterium tuberculosis CYP51. J Inorg Biochem. 2001 Dec 15; 87(4):227-35. PMID: 11744060.
      View in: PubMed
    57. Lepesheva GI, Podust L, Bellamine A, Waterman MR. Folding requirements are different between sterol 14alpha-demethylase (CYP51) from Mycobacterium tuberculosis and human or fungal orthologs. J Biol Chem. 2001 Jul 27; 276(30):28413-20. PMID: 11373285.
      View in: PubMed
    58. Podust L, Poulos TL, Waterman MR. Crystal structure of cytochrome P450 14alpha -sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors. Proc Natl Acad Sci U S A. 2001 Mar 13; 98(6):3068-73. PMID: 11248033; PMCID: PMC30608.
    59. Podust L, Krezel AM, Kim Y. Crystal structure of the CCAAT box/enhancer-binding protein beta activating transcription factor-4 basic leucine zipper heterodimer in the absence of DNA. J Biol Chem. 2001 Jan 05; 276(1):505-13. PMID: 11018027.
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