Structural Basis of Cooperativity in Human UDP-Glucose Dehydrogenase
2011

Understanding Human UDP-Glucose Dehydrogenase Structure

publication Evidence: moderate

Author Information

Author(s): Rajakannan Venkatachalam, Lee Hui-Sun, Chong Seon-Ha, Ryu Han-Bong, Bae Ji-Young, Whang Eun-Young, Huh Jae-Wan, Cho Sung-Woo, Kang Lin-Woo, Choe Han, Robinson Robert C.

Primary Institution: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore

Hypothesis

A better understanding of the conformational changes occurring during the UGDH reaction cycle will pave the way for inhibitor design and potential cancer therapeutics.

Conclusion

The study reveals that the open structure of hUGDH suggests a mechanism for enzyme activity and cooperativity among its subunits.

Supporting Evidence

  • The enzyme UGDH is crucial for converting UDP-glucose to UDP-glucuronic acid.
  • Inhibition of UGDH has been shown to reduce tumor angiogenesis.
  • The study provides insights into the structural basis of enzyme cooperativity.

Takeaway

This study looks at a special enzyme that helps in making important substances in our body, and it shows how the shape of this enzyme changes when it works.

Methodology

The crystal structure of human UGDH in complex with UDP-glucose was solved at 2.8 Å resolution.

Limitations

The open hexamer conformation observed may not represent the major substrate-bound conformation under physiological conditions.

Digital Object Identifier (DOI)

10.1371/journal.pone.0025226

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