Mapping Peptides Correlated with Transmission of Intrasteric Inhibition and Allosteric Activation in Human Cystathionine mages/gifchars/beta2.gif" border="0" align="midd

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• 作者：Suvajit Sen ; Jiong Yu ; Mamoru Yamanishi ; Daniel Schellhorn ; and Ruma Banerjee
• 刊名：Biochemistry
• 出版年：2005
• 出版时间：November 1, 2005
• 年：2005
• 卷：44
• 期：43
• 页码：14210 - 14216
• 全文大小：387K
• 年卷期：v.44,no.43(November 1, 2005)
• ISSN：1520-4995

文摘

Cystathionine mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-synthase plays a key role in the intracellular disposal of homocysteine and isthe single most common locus of mutations associated with homocystinuria. Elevated levels of homocysteineare correlated with heart disease, Alzheimer's and Parkinson's diseases, and neural tube defects.Cystathionine mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-synthase is modular and subjected to complex regulation, but insights into the structuralbasis of this regulation are lacking. We have employed hydrogen exchange mass spectrometry to mappeptides whose motions are correlated with transmission of intrasteric inhibition and allosteric activation.The mass spectrometric data provide an excellent correlation between kinetically and conformationallydistinguishable states of the enzyme. We also demonstrate that a pathogenic regulatory domain mutant,D444N, is conformationally locked in one of two states sampled by the wild type enzyme. Our hydrogenexchange data identify surfaces that are potentially involved in the juxtaposition of the regulatory andcatalytic domains and form the basis of a docked structural model for the full-length enzyme.