Crystal structure of NirD, the small subunit of the nitrite reductase NirbD from Mycobacterium tuberculosis at 2.0 Å resolution

2012 ◽  
Vol 80 (12) ◽  
pp. 2799-2803 ◽  
Author(s):  
Atsushi Izumi ◽  
Robert Schnell ◽  
Gunter Schneider
Keyword(s):  
Crystal Structure ◽  
Mycobacterium Tuberculosis ◽  
Nitrite Reductase ◽  
Small Subunit

scholarly journals Crystal Structure of the [4Fe–4S] Cluster-Containing Adenosine-5′-phosphosulfate Reductase from Mycobacterium tuberculosis

ACS Omega ◽  
2021 ◽  
Author(s):  
Patricia R. Feliciano ◽  
Kate S. Carroll ◽  
Catherine L. Drennan
Keyword(s):  
Crystal Structure ◽  
Mycobacterium Tuberculosis

Crystal Structure of the Mycobacterium tuberculosis dUTPase: Insights into the Catalytic Mechanism

2004 ◽  
Vol 341 (2) ◽  
pp. 503-517 ◽  
Author(s):  
Sum Chan ◽  
Brent Segelke ◽  
Timothy Lekin ◽  
Heike Krupka ◽  
Uhn Soo Cho ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Mycobacterium Tuberculosis ◽  
Catalytic Mechanism

X-ray crystal structure of Mycobacterium tuberculosis haloalkane dehalogenase Rv2579

2008 ◽  
Vol 1784 (2) ◽  
pp. 351-362 ◽  
Author(s):  
Pooja A. Mazumdar ◽  
Jordan C. Hulecki ◽  
Maia M. Cherney ◽  
Craig R. Garen ◽  
Michael N.G. James
Keyword(s):  
Crystal Structure ◽  
Mycobacterium Tuberculosis ◽  
Haloalkane Dehalogenase ◽  
X Ray

scholarly journals The crystal structure of Mycobacterium tuberculosis high-temperature requirement A protein reveals an autoregulatory mechanism

2018 ◽  
Vol 74 (12) ◽  
pp. 803-809
Author(s):  
Arvind Kumar Gupta ◽  
Debashree Behera ◽  
Balasubramanian Gopal
Keyword(s):  
Crystal Structure ◽  
Mycobacterium Tuberculosis ◽  
High Temperature ◽  
Catalytic Domain ◽  
Pdz Domain ◽  
Regulatory Pathways ◽  
Inactive Conformation ◽  
Temperature Requirement ◽  
Autoregulatory Mechanism

The crystal structure of Mycobacterium tuberculosis high-temperature requirement A (HtrA) protein was determined at 1.83 Å resolution. This membrane-associated protease is essential for the survival of M. tuberculosis. The crystal structure reveals that interactions between the PDZ domain and the catalytic domain in HtrA lead to an inactive conformation. This finding is consistent with its proposed role as a regulatory protease that is conditionally activated upon appropriate environmental triggers. The structure provides a basis for directed studies to evaluate the role of this essential protein and the regulatory pathways that are influenced by this protease.

The crystal structure of an essential high-temperature requirement protein HtrA1 (Rv1223) from Mycobacterium tuberculosis reveals its unique features

2018 ◽  
Vol 74 (9) ◽  
pp. 906-921 ◽  
Author(s):  
Khundrakpam Herojit Singh ◽  
Savita Yadav ◽  
Deepak Kumar ◽  
Bichitra Kumar Biswal
Keyword(s):  
Crystal Structure ◽  
Amino Acids ◽  
Mycobacterium Tuberculosis ◽  
High Temperature ◽  
Protein Quality ◽  
Pdz Domain ◽  
Survival Strategies ◽  
Dimensional Structure ◽  
Protease Domain ◽  
Temperature Requirement

High-temperature requirement A (HtrA) proteins, which are members of the heat-shock-induced serine protease family, are involved in extracytoplasmic protein quality control and bacterial survival strategies under stress conditions, and are associated with the virulence of several pathogens; they are therefore major drug targets. Mycobacterium tuberculosis possesses three putative HtrAs: HtrA1 (Rv1223), HtrA2 (Rv0983) and HtrA3 (Rv0125). Each has a cytoplasmic region, a transmembrane helix and a periplasmic region. Here, the crystal structure of the periplasmic region consisting of a protease domain (PD) and a PDZ domain from an M. tuberculosis HtrA1 mutant (mHtrA1S387A) is reported at 2.7 Å resolution. Although the mHtrA1S387A PD shows structural features similar to those of other HtrAs, its loops, particularly L3 and LA, display different conformations. Loop L3 communicates between the PDs of the trimer and the PDZ domains and undergoes a transition from an active to an inactive conformation, as reported for an equivalent HtrA (DegS). Loop LA, which is responsible for higher oligomer formation owing to its length (50 amino acids) in DegP, is very short in mHtrA1S387A (five amino acids), as in mHtrA2 (also five amino acids), and therefore lacks essential interactions for the formation of higher oligomers. Notably, a well ordered loop known as the insertion clamp in the PDZ domain interacts with the protease domain of the adjacent molecule, which possibly aids in the stabilization of a trimeric functional unit of this enzyme. The three-dimensional structure of mHtrA1S387A presented here will be useful in the design of enzyme-specific antituberculosis inhibitors.

Crystal Structure of the TetR/CamR Family Repressor Mycobacterium tuberculosis EthR Implicated in Ethionamide Resistance

2004 ◽  
Vol 340 (5) ◽  
pp. 1095-1105 ◽  
Author(s):  
Lynn G Dover ◽  
Patrick E Corsino ◽  
Ian R Daniels ◽  
Sarah L Cocklin ◽  
Vijaya Tatituri ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Mycobacterium Tuberculosis

scholarly journals Synergistic Lethality of a Binary Inhibitor ofMycobacterium tuberculosisKasA

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Pradeep Kumar ◽  
Glenn C. Capodagli ◽  
Divya Awasthi ◽  
Riju Shrestha ◽  
Karishma Maharaja ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Substrate Binding ◽  
Content Type ◽  
X Ray ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Transcriptional Pattern

ABSTRACTWe report GSK3011724A (DG167) as a binary inhibitor of β-ketoacyl-ACP synthase (KasA) inMycobacterium tuberculosis. Genetic and biochemical studies established KasA as the primary target. The X-ray crystal structure of the KasA-DG167 complex refined to 2.0-Å resolution revealed two interacting DG167 molecules occupying nonidentical sites in the substrate-binding channel of KasA. The binding affinities of KasA to DG167 and its analog, 5g, which binds only once in the substrate-binding channel, were determined, along with the KasA-5g X-ray crystal structure. DG167 strongly augmented thein vitroactivity of isoniazid (INH), leading to synergistic lethality, and also synergized in an acute mouse model ofM. tuberculosisinfection. Synergistic lethality correlated with a unique transcriptional signature, including upregulation of oxidoreductases and downregulation of molecular chaperones. The lead structure-activity relationships (SAR), pharmacokinetic profile, and detailed interactions with the KasA protein that we describe may be applied to evolve a next-generation therapeutic strategy for tuberculosis (TB).IMPORTANCECell wall biosynthesis inhibitors have proven highly effective for treating tuberculosis (TB). We discovered and validated members of the indazole sulfonamide class of small molecules as inhibitors ofMycobacterium tuberculosisKasA—a key component for biosynthesis of the mycolic acid layer of the bacterium’s cell wall and the same pathway as that inhibited by the first-line antitubercular drug isoniazid (INH). One lead compound, DG167, demonstrated synergistic lethality in combination with INH and a transcriptional pattern consistent with bactericidality and loss of persisters. Our results also detail a novel dual-binding mechanism for this compound as well as substantial structure-activity relationships (SAR) that may help in lead optimization activities. Together, these results suggest that KasA inhibition, specifically, that shown by the DG167 series, may be developed into a potent therapy that can synergize with existing antituberculars.

scholarly journals Cytochrome c nitrite reductase from the bacterium Geobacter lovleyi represents a new NrfA subclass

2020 ◽  
Vol 295 (33) ◽  
pp. 11455-11465 ◽  
Author(s):  
Julius Campeciño ◽  
Satyanarayana Lagishetty ◽  
Zdzislaw Wawrzak ◽  
Victor Sosa Alfaro ◽  
Nicolai Lehnert ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Nitrite Reductase ◽  
Nitrate Reduction ◽  
Convergent Evolution ◽  
Nutrient Loss ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Cytochrome C Nitrite Reductase ◽  
Environmental Bacterium ◽  
Key Driver

Cytochrome c nitrite reductase (NrfA) catalyzes the reduction of nitrite to ammonium in the dissimilatory nitrate reduction to ammonium (DNRA) pathway, a process that competes with denitrification, conserves nitrogen, and minimizes nutrient loss in soils. The environmental bacterium Geobacter lovleyi has recently been recognized as a key driver of DNRA in nature, but its enzymatic pathway is still uncharacterized. To address this limitation, here we overexpressed, purified, and characterized G. lovleyi NrfA. We observed that the enzyme crystallizes as a dimer but remains monomeric in solution. Importantly, its crystal structure at 2.55-Å resolution revealed the presence of an arginine residue in the region otherwise occupied by calcium in canonical NrfA enzymes. The presence of EDTA did not affect the activity of G. lovleyi NrfA, and site-directed mutagenesis of this arginine reduced enzymatic activity to <3% of the WT levels. Phylogenetic analysis revealed four separate emergences of Arg-containing NrfA enzymes. Thus, the Ca2+-independent, Arg-containing NrfA from G. lovleyi represents a new subclass of cytochrome c nitrite reductase. Most genera from the exclusive clades of Arg-containing NrfA proteins are also represented in clades containing Ca2+-dependent enzymes, suggesting convergent evolution.

The Crystal Structure of TrpD, a Metabolic Enzyme Essential for Lung Colonization by Mycobacterium tuberculosis, in Complex with its Substrate Phosphoribosylpyrophosphate

2006 ◽  
Vol 355 (4) ◽  
pp. 784-797 ◽  
Author(s):  
Clare E. Lee ◽  
Catherine Goodfellow ◽  
Farah Javid-Majd ◽  
Edward N. Baker ◽  
J. Shaun Lott
Keyword(s):  
Crystal Structure ◽  
Mycobacterium Tuberculosis ◽  
Metabolic Enzyme ◽  
Lung Colonization

scholarly journals Crystal structure of C-terminal desundecapeptide nitrite reductase from Achromobacter cycloclastes

2005 ◽  
Vol 338 (4) ◽  
pp. 1935-1942 ◽  
Author(s):  
Hai-Tao Li ◽  
Tschining Chang ◽  
Wen-Chang Chang ◽  
Chung-Jung Chen ◽  
Ming-Yih Liu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Nitrite Reductase ◽  
Achromobacter Cycloclastes
Sign in / Sign up

Export Citation Format

Share Document