Macromolecular Therapeutics: Development and Delivery Engineering

2016 ◽  
pp. 869-883 ◽  
Author(s):  
Gang Zhao ◽  
Xin Wei ◽  
Dong Wang
Keyword(s):  
Therapeutics Development

scholarly journals Structural insights into SARS-CoV-2 infection and therapeutics development

2021 ◽  
Vol 52 ◽  
pp. 102219
Author(s):  
Gangyu Sun ◽  
Lulu Xue ◽  
Qingjing He ◽  
Yue Zhao ◽  
Wenqing Xu ◽  
...  
Keyword(s):  
Structural Insights ◽  
Therapeutics Development

scholarly journals Rabbit models of human diseases for diagnostics and therapeutics development

2019 ◽  
Vol 92 ◽  
pp. 99-104 ◽  
Author(s):  
Rose G. Mage ◽  
Pedro J. Esteves ◽  
Christoph Rader
Keyword(s):  
Human Diseases ◽  
Therapeutics Development

scholarly journals Enzymatic β-Oxidation of the Cholesterol Side Chain in Mycobacterium Tuberculosis Bifurcates Stereospecifically at Hydration of 3-Oxo-Cholest-4,22- Dien-24-Oyl-CoA

2021 ◽  
Author(s):  
Tianao Yuan ◽  
Joshua Werman ◽  
Xingyu Yin ◽  
Meng Yang ◽  
Miguel Garcia-Diaz ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Fatty Acid ◽  
Alcohol Dehydrogenase ◽  
Side Chain ◽  
Crystallographic Structure ◽  
X Ray ◽  
Steroid Substrate ◽  
Unique Ability ◽  
Therapeutics Development ◽  
Chain Type

<p>The unique ability of <i>Mycobacterium tuberculosis </i>(Mtb) to utilize host lipids such as cholesterol for survival, persistence, and virulence has made the metabolic pathway of cholesterol an area of great interest for therapeutics development, and bioproduction of valuable sterol intermediates. Herein, we identify and characterize two genes from the <a></a><a>Cho-region of the Mtb genome</a>, <i>chsH3 </i>(Rv3538) and <i>chsB1</i> (Rv3502c). Their protein products catalyze <a></a><a>two sequential stereospecific</a>hydration and dehydrogenation steps in the b-oxidation of the cholesterol side chain. ChsH3 favors the <i>22S</i> hydration of 3-oxo-cholest-4,22-dien-24-oyl-CoA in contrast to the previously reported EchA19 (Rv3516) which catalyzes formation of the (<i>22R</i>)-hydroxy-3-oxo-cholest-4-en-24-oyl-CoA from the same enoyl-CoA substrate. ChsB1 is stereospecific and catalyzes dehydrogenation of the ChsH3 product, but not the EchA19 product. The X-ray crystallographic structure of the ChsB1 apo-protein was determined at a resolution of 2.03 Å and the holo-enzyme with bound NAD<sup>+</sup> cofactor at 2.21 Å.The homodimeric structure is representative of a classical NAD<sup>+</sup> utilizing short-chain type alcohol dehydrogenase/reductase, including a Rossmann-fold motif, but exhibits a unique substrate binding site architecture that is of greater length and width than its homologous counterparts, likely to accommodate the bulky steroid substrate. Intriguingly, Mtb utilizes MaoC-like hydratases in sterol side-chain catabolism in contrast to fatty acid b-oxidation in other species that utilize the evolutionarily distinct crotonase family of hydratases. </p>

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