東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Synthesis and Enzymatic Activity of ...

Griswold, Wait Robbins.

Linked to FindBook

Google Book

Amazon

博客來

Synthesis and Enzymatic Activity of 1-Deaza-Pyridoxal 5'-Phosphate: Reinterpreting the Role of the Pyridine Nitrogen in Pyridoxal 5'-Phosphate Utilizing Enzymes.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Synthesis and Enzymatic Activity of 1-Deaza-Pyridoxal 5'-Phosphate: Reinterpreting the Role of the Pyridine Nitrogen in Pyridoxal 5'-Phosphate Utilizing Enzymes./
Author:	Griswold, Wait Robbins.
Description:	176 p.
Notes:	Source: Dissertation Abstracts International, Volume: 72-08, Section: B, page: .
Contained By:	Dissertation Abstracts International72-08B.
Subject:	Chemistry, General. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3456825
ISBN:	9781124665771

Synthesis and Enzymatic Activity of 1-Deaza-Pyridoxal 5'-Phosphate: Reinterpreting the Role of the Pyridine Nitrogen in Pyridoxal 5'-Phosphate Utilizing Enzymes.
Griswold, Wait Robbins.

Synthesis and Enzymatic Activity of 1-Deaza-Pyridoxal 5'-Phosphate: Reinterpreting the Role of the Pyridine Nitrogen in Pyridoxal 5'-Phosphate Utilizing Enzymes. - 176 p.

Source: Dissertation Abstracts International, Volume: 72-08, Section: B, page: .

Thesis (Ph.D.)--University of California, Davis, 2011.

One decade after the fully active phosphorylated form of vitamin B6, pyridoxal 5'-phosphate (PLP), was discovered, a general mechanism for vitamin B6 catalyzed reactions was proposed. Elucidation of the structural features required for enzymatic transamination, racemization, decarboxylation and beta-elimination was made by studying the corresponding non-enzymatic reactions with substituted pyridine and benzene derivatives. Notably, the role of the protonated pyridine ring nitrogen acting as an electron sink in Calpha carbanion stabilization was emphasized. This feature has since become the hallmark of PLP catalyzed reactions as depicted in modern biochemistry textbooks.

ISBN: 9781124665771Subjects--Topical Terms:

1021807
Chemistry, General.

Synthesis and Enzymatic Activity of 1-Deaza-Pyridoxal 5'-Phosphate: Reinterpreting the Role of the Pyridine Nitrogen in Pyridoxal 5'-Phosphate Utilizing Enzymes.
LDR:03578nam 2200373 4500 001 1405561
005 20111219143102.5
008 130515s2011 ||||||||||||||||| ||eng d
020 $a 9781124665771
035 $a (UMI)AAI3456825
035 $a AAI3456825
040 $a UMI $c UMI
100 1 $a Griswold, Wait Robbins. $3 1684948
245 1 0 $a Synthesis and Enzymatic Activity of 1-Deaza-Pyridoxal 5'-Phosphate: Reinterpreting the Role of the Pyridine Nitrogen in Pyridoxal 5'-Phosphate Utilizing Enzymes.
300 $a 176 p.
500 $a Source: Dissertation Abstracts International, Volume: 72-08, Section: B, page: .
500 $a Adviser: Michael D. Toney.
502 $a Thesis (Ph.D.)--University of California, Davis, 2011.
520 $a One decade after the fully active phosphorylated form of vitamin B6, pyridoxal 5'-phosphate (PLP), was discovered, a general mechanism for vitamin B6 catalyzed reactions was proposed. Elucidation of the structural features required for enzymatic transamination, racemization, decarboxylation and beta-elimination was made by studying the corresponding non-enzymatic reactions with substituted pyridine and benzene derivatives. Notably, the role of the protonated pyridine ring nitrogen acting as an electron sink in Calpha carbanion stabilization was emphasized. This feature has since become the hallmark of PLP catalyzed reactions as depicted in modern biochemistry textbooks.
520 $a In order to further understand the role of the pyridine nitrogen and to investigate the extent to which PLP utilizing enzymes depend upon the electron sink properties of PLP, the first synthesis of the isosteric carbocyclic analogue of PLP, 1-deaza-pyridoxal 5'-phosphate, (deaza-PLP) was undertaken (Chapter 2).
520 $a The very low catalytic activity of aspartate aminotransferase reconstituted with deaza-PLP toward L-aspartate allowed the 1.8 A resolution crystal structure of the stable external aldimine to be obtained (Chapter 3).
520 $a Experiments with the catalytically inactive K258A aspartate aminotransferase mutant provide direct evidence, through measurement of an equilibrium isotope effect, for ground state destabilization due to hyperconjugation in the L-aspartate external aldimine. The much smaller equilibrium isotope effect obtained with deaza-PLP aspartate aminotransferase indicates that the pyridine ring nitrogen plays a crucial role in labilizing the Calpha-H sigma bond in this enzyme (Chapter 4).
520 $a Finally, the supposedly requisite role played by the protonated pyridine ring nitrogen in the reaction mechanisms of other classes of PLP enzymes was investigated. The extent of protonation of the pyridine ring nitrogen of PLP, and thus its electron sink properties, is expected to vary with the acidity of the residue interacting with it. Aspartate aminotransferase fully protonates the pyridine ring nitrogen, while alanine racemase and O-acetylserine sulfhydrylase both maintain a neutral cofactor ring. Reconstitution of these three enzymes with deaza-PLP indicates that the pyridine ring nitrogen is essential for the 1, 3-prototropic shift in transamination but not for beta-elimination (Chapter 5).
590 $a School code: 0029.
650 4 $a Chemistry, General. $3 1021807
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Chemistry, Organic. $3 516206
650 4 $a Health Sciences, Nutrition. $3 1017801
690 $a 0485
690 $a 0487
690 $a 0490
690 $a 0570
710 2 $a University of California, Davis. $b Chemistry. $3 1679244
773 0 $t Dissertation Abstracts International $g 72-08B.
790 1 0 $a Toney, Michael D., $e advisor
790 1 0 $a Fisher, Andrew J. $e committee member
790 1 0 $a Chen, Xi $e committee member
790 $a 0029
791 $a Ph.D.
792 $a 2011
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3456825