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データを開く
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基本情報
登録情報 | データベース: SASBDB / ID: SASDD33 |
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![]() | Toxin/Antitoxin complex from M. tuberculosis
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機能・相同性 | Antitoxin Xre/MbcA/ParS-like, toxin-binding domain / Antitoxin Xre/MbcA/ParS C-terminal toxin-binding domain / RES domain / RES domain / RES / 転移酵素; グリコシル基を移すもの; 五炭糖残基を移すもの / nucleotidyltransferase activity / Mycobacterial cidal antitoxin MbcA / NAD(+) phosphorylase MbcT![]() |
生物種 | ![]() |
![]() | ![]() タイトル: An NAD Phosphorylase Toxin Triggers Mycobacterium tuberculosis Cell Death. 著者: Diana Mendes Freire / Claude Gutierrez / Acely Garza-Garcia / Anna D Grabowska / Ambre J Sala / Kanchiyaphat Ariyachaokun / Terezie Panikova / Katherine S H Beckham / André Colom / Vivian ...著者: Diana Mendes Freire / Claude Gutierrez / Acely Garza-Garcia / Anna D Grabowska / Ambre J Sala / Kanchiyaphat Ariyachaokun / Terezie Panikova / Katherine S H Beckham / André Colom / Vivian Pogenberg / Michele Cianci / Anne Tuukkanen / Yves-Marie Boudehen / Antonio Peixoto / Laure Botella / Dmitri I Svergun / Dirk Schnappinger / Thomas R Schneider / Pierre Genevaux / Luiz Pedro Sorio de Carvalho / Matthias Wilmanns / Annabel H A Parret / Olivier Neyrolles / ![]() ![]() ![]() ![]() 要旨: Toxin-antitoxin (TA) systems regulate fundamental cellular processes in bacteria and represent potential therapeutic targets. We report a new RES-Xre TA system in multiple human pathogens, including ...Toxin-antitoxin (TA) systems regulate fundamental cellular processes in bacteria and represent potential therapeutic targets. We report a new RES-Xre TA system in multiple human pathogens, including Mycobacterium tuberculosis. The toxin, MbcT, is bactericidal unless neutralized by its antitoxin MbcA. To investigate the mechanism, we solved the 1.8 Å-resolution crystal structure of the MbcTA complex. We found that MbcT resembles secreted NAD-dependent bacterial exotoxins, such as diphtheria toxin. Indeed, MbcT catalyzes NAD degradation in vitro and in vivo. Unexpectedly, the reaction is stimulated by inorganic phosphate, and our data reveal that MbcT is a NAD phosphorylase. In the absence of MbcA, MbcT triggers rapid M. tuberculosis cell death, which reduces mycobacterial survival in macrophages and prolongs the survival of infected mice. Our study expands the molecular activities employed by bacterial TA modules and uncovers a new class of enzymes that could be exploited to treat tuberculosis and other infectious diseases. |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
-モデル
モデル #1743 | ![]() タイプ: atomic / ダミー原子の半径: 1.90 A / カイ2乗値: 1.007 / P-value: 0.259841 ![]() |
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モデル #1745 | ![]() タイプ: dummy / ダミー原子の半径: 2.50 A / 対称性: P1 / カイ2乗値: 0.969 / P-value: 0.080559 ![]() |
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試料
![]() | 名称: Toxin/Antitoxin complex from M. tuberculosis / 試料濃度: 0.63 mg/ml / Entity id: 948 / 949 |
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バッファ | 名称: 100 mM HEPES, 100 mM NaCl / pH: 7.5 |
要素 #948 | 名称: MbcT / タイプ: protein / 記述: Mycobacterial cidal toxin / 分子量: 20.248 / 分子数: 6 由来: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) 参照: UniProt: P9WLP9 配列: VSDALDEGLV QRIDARGTIE WSETCYRYTG AHRDALSGEG ARRFGGRWNP PLLFPAIYLA DSAQACMVEV ERAAQAASTT AEKMLEAAYR LHTIDVTDLA VLDLTTPQAR EAVGLENDDI YGDDWSGCQA VGHAAWFLHM QGVLVPAAGG VGLVVTAYEQ RTRPGQLQLR QSVDLTPALY QELRAT |
要素 #949 | 名称: MbcA / タイプ: protein / 記述: Mycobacterial cidal antitoxin / 分子量: 12.616 / 分子数: 6 由来: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) 参照: UniProt: P9WLP7 配列: GAMGVNVLAS TVSGAIERLG LTYEEVGDIV DASPRSVARW TAGQVVPQRL NKQRLIELAY VADALAEVLP RDQANVWMFS PNRLLEHRKP ADLVRDGEYQ RVLALIDAMA EGVFV |
-実験情報
ビーム | 設備名称: PETRA III EMBL P12 / 地域: Hamburg / 国: Germany ![]() | |||||||||||||||||||||||||||||||||||||||
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検出器 | 名称: Pilatus 2M | |||||||||||||||||||||||||||||||||||||||
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