scholarly journals Structure-function studies of CrmK, an oxidase involved in Caerulomycin A biosynthesis

2014 ◽  
Vol 70 (a1) ◽  
pp. C1669-C1669
Author(s):  
Marie-Ève Picard ◽  
Julie Barma ◽  
Yiguang Zhu ◽  
Xavier Murphy Després ◽  
Jean-Baptiste Duvignaud ◽  
...  

Caerulomycin A (CRM A) is an immunosupressive agent that has a unique 2,2'-bipyridine core structure. Isolated from a marine-derived Actinoalloteichus cyanogriseus, this natural product exhibits antifungal, anti-amoebic, antitumor, and antimicrobial activities. Its biosynthetic pathway consists of more than 20 enzymes, at least seven of which are putatively involved in post-PKS/NRPS modifications of the scaffold. Among these, CrmK is a flavin-dependent oxidase. We have determined the crystal structure of CrmK bound to its flavin adenin dinucleotide (FAD) cofactor at 1.9 Å resolution. FAD linkage to CrmK is observed via two covalent bonds with protein residues His64 and Cys124. This crystal structure, combined with the activity analysis of both wild-type CrmK and a series of mutants, has revealed the role of active site residues lining the substrate and FAD binding pocket. Our studies add additional molecular insights into the structure and function relationship of the bicovalently flavinylated oxidases.

Biochemistry ◽  
2011 ◽  
Vol 50 (39) ◽  
pp. 8352-8361 ◽  
Author(s):  
Alessia Belgi ◽  
Mohammed A. Hossain ◽  
Fazel Shabanpoor ◽  
Linda Chan ◽  
Suode Zhang ◽  
...  

2020 ◽  
Vol 129 (5) ◽  
pp. 1024-1032
Author(s):  
Hannah J. Thomas ◽  
Usaid Rana ◽  
Channa E. Marsh ◽  
Harrison T. Caddy ◽  
Lachlan J. Kelsey ◽  
...  

There is acknowledged variability in the Circle of Willis in the general population, yet the structure and function relationship of the cerebrovasculature is poorly understood. Using a combination of magnetic resonance imaging, high-resolution Doppler ultrasound, and computational fluid dynamic modeling, we show that monozygotic twins exhibit differences in cerebrovascular structure and function when exposed to physiological stimuli. These data suggest that the morphology, function, and health of cerebrovascular arteries are not primarily genetically determined.


2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Meng Zhang

Human phospholipid transfer protein (PLTP) mediates the transfer of lipids among atheroprotective high-density lipoproteins (HDL) and atherogenic low-density lipoproteins (LDL) by an unknown mechanism. Delineating this mechanism would be an important step toward the understanding and regulation of PLTP for treating cardiovascular diseases, hypoalphalipoproteinemia and hyperalphalipoproteinemia. Using electron microscopy, negative-staining, and single-particle image processing, we discovered that PLTP penetrates each class of HDL, LDL and liposome independently, and also bridges a ternary complex with one of its distal end-domains penetrating into HDL and another distal domain interacting with LDL. These new insights into PLTP interaction with lipoproteins and liposomes provide a molecular basis for analyzing PLTP-dependent lipid transfer between lipoprotein particles.


1987 ◽  
Vol 6 (1) ◽  
Author(s):  
Shun-Ichiro Kawabata ◽  
Takashi Morita ◽  
Toshiyuki Miyata ◽  
Shigenori Kaida ◽  
Sadaaki Iwanaga ◽  
...  

Placenta ◽  
1998 ◽  
Vol 19 (7) ◽  
pp. A21
Author(s):  
A. Sato ◽  
T. Otani ◽  
T. Maruo ◽  
A.J.W. Hsueh ◽  
I. Boime

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