Structural insights into inhibition of the drug target dihydroorotate dehydrogenase by bacterial hydroxyalkylquinolines

被引：6
|
作者：
Horwitz, Samantha M. [1 ]
Blue, Tamra C. [1 ]
Ambarian, Joseph A. [1 ]
Hoshino, Shotaro [2 ]
Seyedsayamdost, Mohammad R. [2 ]
Davis, Katherine M. [1 ]
机构：
[1] Emory Univ, Dept Chem, Atlanta, GA 30322 USA
[2] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA
来源：
RSC CHEMICAL BIOLOGY | 2022年 / 3卷 / 04期
基金：
美国国家卫生研究院;
关键词：
NATURAL-PRODUCTS; BURKHOLDERIA-PSEUDOMALLEI; FLAVIN REDUCTION; BINDING; REVEALS; IDENTIFICATION; DERIVATIVES; RESISTANCE; MECHANISM; DESIGN;
D O I：
10.1039/d1cb00255d
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Hydroxyalkylquinolines (HAQs) are ubiquitious natural products but their interactions with associated protein targets remain elusive. We report X-ray crystal structures of two HAQs in complex with dihydroorotate dehydrogenase (DHODH). Our results reveal the structural basis of DHODH inhibition by HAQs and open the door to downstream structure-activity relationship studies.
引用
收藏
页码：420 / 425
页数：6
相关论文
共 50 条
  • [21] Structural insights into TRPM8 inhibition and desensitization
    Diver, Melinda M.
    Cheng, Yifan
    Julius, David
    SCIENCE, 2019, 365 (6460) : 1434 - +
  • [22] Structural insights into the bacterial carbon-phosphorus lyase machinery
    Seweryn, Paulina
    Van, Lan Bich
    Kjeldgaard, Morten
    Russo, Christopher J.
    Passmore, Lori A.
    Hove-Jensen, Bjarne
    Jochimsen, Bjarne
    Brodersen, Ditlev E.
    NATURE, 2015, 525 (7567) : 68 - +
  • [23] Mechanistic and Structural Insights into the Specificity and Biological Functions of Bacterial Sulfoglycosidases
    Zhang, Zhen
    Dong, Mochen
    Zallot, Remi
    Blackburn, George Michael
    Wang, Nini
    Wang, Chengjian
    Chen, Long
    Baumann, Patrick
    Wu, Zuyan
    Wang, Zhongfu
    Fan, Haiming
    Roth, Christian
    Jin, Yi
    He, Yuan
    ACS CATALYSIS, 2023, 13 (01) : 824 - 836
  • [24] Structural Characterization of Neisseria gonorrhoeae Bacterial Peroxidase-Insights into the Catalytic Cycle of Bacterial Peroxidases
    Nobrega, Claudia S.
    Carvalho, Ana Luisa
    Romao, Maria Joao
    Pauleta, Sofia R.
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023, 24 (07)
  • [25] Structural Insights into Substrate Binding and Antibiotic Inhibition of Enterobacterial Penicillin-Binding Protein 6
    Salleh, Mohd Zulkifli
    Singh, Kirnpal Kaur Banga
    Deris, Zakuan Zainy
    LIFE-BASEL, 2022, 12 (07):
  • [26] Structural insights into the inhibition of glycine reuptake
    Shahsavar, Azadeh
    Stohler, Peter
    Bourenkov, Gleb
    Zimmermann, Iwan
    Siegrist, Martin
    Guba, Wolfgang
    Pinard, Emmanuel
    Sinning, Steffen
    Seeger, Markus A.
    Schneider, Thomas R.
    Dawson, Roger J. P.
    Nissen, Poul
    NATURE, 2021, 591 (7851) : 677 - +
  • [27] Inhibitory effects and structural insights for a novel series of coumarin-based compounds that selectively target human CA IX and CA XII carbonic anhydrases
    De Luca, Laura
    Mancuso, Francesca
    Ferro, Stefania
    Buemi, Maria Rosa
    Angeli, Andrea
    Del Prete, Sonia
    Capasso, Clemente
    Supuran, Claudiu T.
    Gitto, Rosaria
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 143 : 276 - 282
  • [28] Structural insights of AKT and its activation mechanism for drug development
    Kumar, B. Harish
    Kabekkodu, Shama Prasada
    Pai, K. Sreedhara Ranganath
    MOLECULAR DIVERSITY, 2025,
  • [29] A Triazolopyrimidine-Based Dihydroorotate Dehydrogenase Inhibitor with Improved Drug-like Properties for Treatment and Prevention of Malaria
    Phillips, Margaret A.
    White, Karen L.
    Kokkonda, Sreekanth
    Deng, Xiaoyi
    White, John
    El Mazouni, Farah
    Marsh, Kennan
    Tomchick, Diana R.
    Manjalanagara, Krishne
    Rudra, Kakali Rani
    Wirjanata, Grennady
    Noviyanti, Rintis
    Price, Ric N.
    Marfurt, Jutta
    Shackleford, David M.
    Chiu, Francis C. K.
    Campbell, Michael
    Jimenez-Diaz, Maria Belen
    Bazaga, Santiago Ferrer
    Angulo-Barturen, Inigo
    Martinez, Maria Santos
    Lafuente-Monasterio, Maria
    Kaminsky, Werner
    Silue, Kigbafori
    Zeeman, Anne-Marie
    Kocken, Clemens
    Leroy, Didier
    Blasco, Benjamin
    Rossignol, Emilie
    Rueckle, Thomas
    Matthews, Dave
    Burrows, Jeremy N.
    Palmer, Michael J.
    Rathod, Pradipsinh K.
    Charman, Susan A.
    ACS INFECTIOUS DISEASES, 2016, 2 (12): : 57 - 69
  • [30] Dihydroorotate dehydrogenase Inhibitors Target c-Myc and Arrest Melanoma, Myeloma and Lymphoma cells at S-phase
    Dorasamy, Mathura Subangari
    Choudhary, Bhavesh
    Nellore, Kavitha
    Subramanya, Hosahalli
    Wong, Pooi-Fong
    JOURNAL OF CANCER, 2017, 8 (15): : 3086 - 3098
12345