Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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A Molecular Modeling Study of AAD16034

  • Cho, Hoon (Research Center for Resistant Cells, Chosun University) ;
  • Choi, Cheol-Hee (Research Center for Resistant Cells, Chosun University) ;
  • Yoo, Kyung-Ho (Korea Instutute of Science and Technology) ;
  • Cho, Seung-Joo (Research Center for Resistant Cells, Chosun University)
  • Published : 2008.12.31
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Abstract

AAD16034 is an alginate lyase from Pseudoalteromonas sp. IAM14594. A very close homologue with known 3D structure exists (marine bacterium Pseudoalteromonas sp. strain no. 272). A three-dimensional structure of AAD16034 was generated based on this template (PDB code: 1J1T) by comparative modeling. The modeled enzyme exhibited a jelly-roll like structure very similar to its template structure. Both enzymes possess the characteristic alginate sequence YFKhG+Y-Q. Since AAD16034 displays enzymatic activity for poly-M alginate, docking of a tri-mannuronate into the modeled structure was performed. Two separate and adjacent binding sites were found. The ligand was accommodated inside each binding site. By considering both binding sites, a plausible binding pose for the poly-M alginate polymer could be deduced. From the modeled docking pose (i.e., the most important factor that attracts alginate polymer into this lyase) the most likely interaction was electrostatic. In accordance with a previous report, the hydroxyl group of Y345 was positioned close to the ${\alpha}$-hydrogen of ${\beta}$-mannuronate, which was suitable to initiate a ${\beta}$-elimination reaction. K347 was also very near to the carboxylatemoiety of the ligand, which might stabilize the dianion intermediate during the ${\beta}$-elimination reaction. This implies that the characteristic alginate sequence is absolutely crucial for the catalysis. These results may be exploited in the design of novel enzymes with desired properties.

Keywords

References

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