Studies of porphyrin biosynthetic enzymes : structural and mechanistic studies of PBG deaminase and production of uroporphyrinogen III synthase /

Bibliographic Details
Main Author: Clemens, Karen Reiter, 1963-
Other Authors: Hogg, John L. (degree committee member.), Pace, Carlos N. (degree committee member.), Raushel, Frank M. (degree committee member.)
Format: Thesis Book
Language:English
Published: 1991.
Subjects:
Online Access:ProQuest, Abstract
Link to OAKTrust copy
Description
Abstract:In structure-activity studies conducted with PBG deaminase, substituents on the periphery of the pyrrole ring were varied to test the fidelity and structural requirements of the enzyme. Analogs with different arrangements of side chains at C-3 and C-4, showed that an acidic side chain at C-4 is required for covalent interaction with the enzyme. PBG derivatives exhibit unimolecular activation through either a concerted 1 , 6 -elimination or an El-like mechanism. Solvolysis of model compounds supports the possibility that PBG may react similarly. Structural studies of PBG deaminase were conducted with wild-type holoenzyme, apoenzyme, two histidine mutants, and proteolytic products. It was shown that the cofactor serves a major structural role. Effects of histidine mutations on the catalytic activity were minor, in contrast to the inactivation caused by proteolysis. A plasmid was constructed for expression of uro'gen III synthase.
Item Description:Typescript (photocopy).
Vita.
"Major subject: Chemistry."
Physical Description:xi, 146 leaves : illustrations ; 29 cm
Bibliography:Includes bibliographical references.