Modulating the function of human serine racemase and human serine dehydratase by protein engineering

Cyong Yi Wang, Shan Chi Ku, Cheng Chung Lee, Andrew H.J. Wang

研究成果: 雜誌貢獻文章同行評審

7 引文 斯高帕斯(Scopus)

摘要

d-Serine is a co-agonist of N-methyl d-aspartate, a glutamate receptor, which is a major excitatory neurotransmitter receptor in the brain. Human serine racemase (hSR) and serine dehydratase (hSDH) are two important pyridoxal-5′-phosphate-dependent enzymes that synthesize and degrade d-serine, respectively. hSR and hSDH have significant sequence homology (28 identity) and are similar in their structural folds (root-mean-square deviation, 1.12 Å). Sequence alignment and structural comparison between hSR and hSDH reveal that S84 in hSR and A65 in hSDH play important roles in their respective enzyme activities. We surmise that exchange of these two amino acids by introducing S84A hSR and A65S hSDH mutants may result in switching their protein functions. To understand the modulating mechanism of the key residues, mutants S84A in hSR and A65S in hSDH were constructed to monitor the change of activities. The structure of A65S hSDH mutant was determined at 1.3 Å resolution (PDB 4H27), elucidating the role of this critical amino acid. Our study demonstrated S84A hSR mutant behaved like hSDH, whereas A65S hSDH mutant acquired an additional function of using d-serine as a substrate.
原文英語
頁(從 - 到)741-749
頁數9
期刊Protein Engineering, Design and Selection
25
發行號11
DOIs
出版狀態已發佈 - 11月 2012
對外發佈

ASJC Scopus subject areas

  • 生物技術
  • 生物工程
  • 生物化學
  • 分子生物學

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