Structural and functional comparisons between OTCase and ATCase, leading to the formation and characterization of an active "domain fusion" between argI (OTCase) and pyrB (ATCase) /

Bibliographic Details
Main Author: Houghton, John Edgar, 1960-
Other Authors: Peterson, David O. (degree committee member.), Pettigrew, Donald W. (degree committee member.), Young, Ryland F. (degree committee member.)
Format: Thesis Book
Language:English
Published: 1986.
Subjects:
Online Access:Link to ProQuest copy
Link to OAKTrust copy

MARC

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099 |a 1986  |a Disser-  |a tation  |a H838 
100 1 |a Houghton, John Edgar,  |d 1960- 
245 1 0 |a Structural and functional comparisons between OTCase and ATCase, leading to the formation and characterization of an active "domain fusion" between argI (OTCase) and pyrB (ATCase) / 
264 1 |c 1986. 
300 |a xiv, 140 leaves :  |b illustrations ;  |c 29 cm 
336 |a text  |b txt  |2 rdacontent 
337 |a unmediated  |b n  |2 rdamedia 
338 |a volume  |b nc  |2 rdacarrier 
500 |a "Major subject: Biochemistry." 
500 |a Typescript (photocopy). 
500 |a Vita. 
502 |b Ph. D.  |c Texas A & M University  |d 1986 
504 |a Includes bibliographical references (leaves 114-122). 
520 3 |a Aspartate Transcarbamoylase (ATCase, carbamoylphosphate: L-aspartate carbamoyltransferase, EC 2.1.3.2) and Ornithine transcarbamoylase (OTCase, carbamoylphosphate: L-ornithine carbamoyltransferase, EC 2.1.3.3) both catalyze the transfer of a carbamoyl moiety from carbamoyl phosphate to an amino acid (aspartate and ornithine, respectively). In addition the two enzymes exhibit a number of similar physical and chemical properties, which suggest that these two systems may share a common heritage, a phenomenon which might be exhibited in conservation of primary sequence and structure. Reported herein is a comparison of the primary sequences of ATCase and OTCase, which was undertaken to confirm the existence of such an evolutionary link. In addition, using Chou-Fasman predictive analysis [Chou, P. Y. & Fasman, G. D. (1974) Biochemistry 13, 211-222; 222-245] a comparison of predicted secondary structural properties was undertaken to correlate similar physical and enzymatic characteristics with the discrete primary and secondary structures of the two enzymes. These analyses revealed numerous primary and predicted secondary structural similarities, which do indeed support the contention that these two systems have evolved from a common ancestor. Moreover, it became apparent that the conservation of residues was not uniformly distributed throughout the two peptide sequences but was more rigorous within the N-terminal portion of the primary sequences of both enzymes, as was the predicted secondary structural homology. This region is known to comprise a stable and well defined tertiary structure, the polar domain, in ATCase. Such conservation of sequence and structure promoted speculation as to the possibility that this polar domain might readily be substituted for by the corresponding homologous region of OTCase. Such a substitution was engineered through recombinant DNA technology and was indeed found to encode an active, though drastically impaired, aspartate transcarbamoylating enzyme. 
650 0 |a Enzymatic analysis. 
650 0 |a Molecular genetics. 
650 4 |a Major biochemistry. 
655 7 |a Academic theses  |2 lcgft 
700 1 |a O'Donovan, Gerard A.,  |e degree supervisor. 
700 1 |a Peterson, David O.,  |e degree committee member. 
700 1 |a Pettigrew, Donald W.,  |e degree committee member. 
700 1 |a Wild, James R.,  |e degree supervisor. 
700 1 |a Young, Ryland F.,  |e degree committee member. 
710 2 |a Texas A & M University,  |e degree granting institution. 
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856 4 1 |u https://hdl.handle.net/1969.1/DISSERTATIONS-23175  |z Link to OAKTrust copy  |t 0 
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