2007 Fiscal Year Final Research Report Summary
Regulation of Protein Functions by Hume and CBS Domain
| Project/Area Number |
17550156
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemistry related to living body
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| Research Institution | Yamaguchi University |
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Principal Investigator |
OZAKI Shin-ichi Yamaguchi University, Faculty of Agriculture, Associate Professor (40280581)
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| Co-Investigator(Kenkyū-buntansha) |
MIGITA Taiko Yamaguchi University, Faculty of Agriculture, Professor (90159161)
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| Project Period (FY) |
2005 – 2007
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| Keywords | heme / Vitamin B6 |
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| Research Abstract |
Human cystathionine b-synthase (CBS) catalyzes a pyridoxal 5-phosphate (PLP)dependent b-replacement reaction to synthesize cystathionine from serine and homocysteine. The enzyme is unique in bearing not only a catalytically important PLP but also heme. In this study, we have found that (1) the alternation of heme coordination under the alkaline condition inactivate the enzyme by approximately half, and (2) the mutagenesis of Arg-5 I and Arg-224 with Ala decreases CBS activity by half, and the replacement of Arg-266 with Ala or Glu generates heme-free almost inactive enzymes. The results clearly indicate that the heme environment has to be appropriately organized to exhibit the maximum CBS activity although heme is located 20 A away from PLP in the active site. Furthermore, the crystal structure of CBS indicates that Arg-266 would have electrostatic interaction with Cys, one of the proximal ligands for heme iron. We propose that Arg-266 is an important residue for the communication between heme and PLP in CBS.
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