Structure function diversity within the phosphoenolpyruvate mutase/isocitrate lyase superfamily as r...

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" Structure function diversity within the phosphoenolpyruvate mutase/isocitrate lyase superfamily as revealed by the enzymes oxaloacetate decarboxylase and 2,3-dimethylmalate lyase "
Buvaneswari Coimbatore Narayanan O. Herzberg

Document Type	:	Latin Dissertation
Language of Document	:	English
Record Number	:	53298
Doc. No	:	TL23252
Call number	:	‭3359411‬
Main Entry	:	Buvaneswari Coimbatore Narayanan
Title & Author	:	Structure function diversity within the phosphoenolpyruvate mutase/isocitrate lyase superfamily as revealed by the enzymes oxaloacetate decarboxylase and 2,3-dimethylmalate lyase\ Buvaneswari Coimbatore Narayanan
College	:	University of Maryland, College Park
Date	:	2008
Degree	:	Ph.D.
student score	:	2008
Page No	:	140
Abstract	:	Two members of the phosphoenolpyruvate mutase (PEPM)/isocitrate lyase (ICL) superfamily were investigated to study their structure-function relationships and to identify sequence signatures that define a particular function. The first enzyme (PA4872) was a protein of unknown function from Pseudomonas aeruginosa. The second enzyme from Aspergillus niger (An07g08390) was thought to be an oxaloacetate acetyl hydrolase (OAH) because of its high sequence identity (∼60%) to an enzyme with confirmed OAH activity. The X-ray crystal structure determination of PA4872 revealed unique features that guided the design of biochemical experiments, which ultimately led to the discovery that the enzyme is an oxaloacetate decarboxylase (OAD). Two structures of An07g08390, one with bound Mg 2+ and the second with bound Mn2+ and the inhibitor 3,3-difluorooxaloacetate, were determined. The functional studies demonstrated that although the enzyme has OAH activity, it has a far better activity as a 2R,3S-dimethylmalate lyase (DMML). The active site structure of DMML indicated a proline residue (Pro240) as a marker of DMML function along with confirming the conserved locations of previously established signature residues for lyase activity. OAD is the founding member of a family within the PEPM/ICL superfamily and thus defines the function of the remaining family members. However, the biological context in which OAD functions remains unknown. DMML is known to function in the nicotinate catabolism pathway but not all the members of the pathway are present in A. niger. Transcriptome analysis suggests that the DMML encoding gene is under carbon catabolite repression but the pathway in which the enzyme functions has not yet been identified.
Subject	:	Biological sciences; Oxaloacetate decarboxylase; Phosphoenolpyruvate mutase; Isocitrate lyase; Dimethylmalate lyase; Biophysics; 0786:Biophysics
Added Entry	:	O. Herzberg
Added Entry	:	University of Maryland, College Park