Table Of Content1
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7 ACS SYMPOSIUM SERIES
ACS
SYMPOSIUM
SERIES BM B MECHANISTIC
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VOLUME 1357 H O
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INAN GIC ENZYMOLOGY
GI A
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ST
TI BRIDGING STRUCTURE AND FUNCTION
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THEORETICAL, COMPUTATIONAL, AND U E
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EXPERIMENTAL PERSPECTIVES TZ
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Mechanistic enzymology is the basis of many applications, from drug AL
NO
design to cleaning products. This work offers a timely synopsis of advanced
DG
understanding of enzymatic regulation and function. Chapters are authored Y
F
by both those in traditional protein studies and those challenging paradigms, U
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bridging disconnected fields, and presenting a unified view of enzyme
C
mechanisms. Biochemists, structural biologists, and other researchers T
I
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working with enzymes will find this work useful. Each chapter is written to
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maximize accessibility to students and bridge developed theory with current
scientific literature. This work serves as a valuable teaching tool to introduce
foundational topics to students, bridging distantly connected fields toward the
presentation of a unified view of enzyme mechanism.
PUBLISHED BY THE
American Chemical Society
MILLER
M
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Mechanistic Enzymology:
Bridging Structure and Function
1357
ACS SYMPOSIUM SERIES
Mechanistic Enzymology:
Bridging Structure and Function
Justin M. Miller,Editor
Middle Tennessee State University - Chemistry
1301 East Main Street
Murfreesboro, Tennessee, United States
American Chemical Society, Washington, DC
Library of Congress Cataloging-in-Publication Data
Names: Miller, Justin M., editor.
Title: Mechanistic enzymology : bridging structure and function / Justin M.
Miller, editor, Middle Tennessee State University -- Chemistry, 1301
East Main Street Murfreesboro, Tennessee, United States.
Description: Washington, DC : American Chemical Society, [2020] | Series:
Acs symposium series ; 1357 | Includes bibliographical references and
index.
Identifiers: LCCN 2020034013 (print) | LCCN 2020034014 (ebook) | ISBN
9780841298842 (hardcover) | ISBN 9780841298835 (ebook other)
Subjects: LCSH: Enzymology.
Classification: LCC QP601 .M438 2020 (print) | LCC QP601 (ebook) | DDC
612/.0151--dc23
LC record available at https://lccn.loc.gov/2020034013
LC ebook record available at https://lccn.loc.gov/2020034014
ThepaperusedinthispublicationmeetstheminimumrequirementsofAmericanNationalStandardforInformation
Sciences—Permanence of Paper for Printed Library Materials, ANSI Z39.48n1984.
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Foreword
TheACSSymposiumSeriesisanestablishedprogramthatpublisheshigh-qualityvolumesof
thematicmanuscripts.Forover40years,theACSSymposiumSerieshasbeendeliveringessential
research from world leading scientists, including 36 Chemistry Nobel Laureates, to audiences
spanning disciplines and applications.
BooksaredevelopedfromsuccessfulsymposiasponsoredbytheACSorotherorganizations.
Topics span the entirety of chemistry, including applications, basic research, and interdisciplinary
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Beforeagreeingtopublishabook,prospectiveeditorssubmitaproposal,includingatableof
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comprehensiveness. All chapters are peer reviewed prior to final acceptance or rejection.
Asarule,onlyoriginalresearchpapersandoriginalreviewpapersareincludedinthevolumes.
Verbatim reproductions of previous published papers are not accepted.
ACS Books
Contents
1. Introduction: Viewing Science through Multiple Lenses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Justin M. Miller
2. Enzyme Active Site Architecture: The Whole Is Greater Than the Sum of the Parts. . . . . . 9
Justin M. Miller and Chad Brambley
3. Integrative Structural Biology: Using X-ray Crystallography, Small-Angle X-ray
Scattering, and Cryogenic Electron Microscopy to Determine Protein Structures. . . . . . . 31
Jamie R. Wallen
4. Evolving Role of Conformational Dynamics in Understanding Fundamental
Biomolecular Behavior. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
David Ban
5. KatG Structure and Mechanism: Using Protein-Based Oxidation to Confront the
Threats of Reactive Oxygen. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Jessica R. Krewall, Laura E. Minton, and Douglas C. Goodwin
6. Understanding Enzyme Catalysis Mechanism Using QM/MM Simulation Methods. . . 121
Tao Yu and Hong Guo
7. Tunneling through the Barriers: Resolving the Origins of the Activation of C-H
Bonds Catalyzed by Enzymes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Chris Whittington, John Latham, and Adam R. Offenbacher
8. Enzymatic Biodegradation by Exploring the Rational Protein Engineering of the
Polyethylene Terephthalate Hydrolyzing Enzyme PETase fromIdeonella sakaiensis
201-F6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Mitch H. Weiland
Editor Biography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Indexes
Author Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
Subject Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
vii
Chapter1
Introduction: Viewing Science through Multiple Lenses
Justin M.Miller
Middle Tennessee State University, Department of Chemistry, 1301 East Main Street,
Murfreesboro, Tennessee 37132, United States of America
*Email:[email protected]
It affirms…that the same is true for the steps from electrons to atoms, from atoms to
molecules, from molecules to crystals. It holds that the properties of atoms do indeed
dependonthosewhichtheelectronshavewhentheyareintheatoms;thepropertiesof
moleculesonthosewhichtheatomshavewhentheyareinthemolecules.Itholdstoothat
thepropertiesoflivingthingsdependonthoseoftheirphysicalconstituentswhenthelatter
areinlivingthings;theactivitiesofthinkingbeingsontheactionoftheirphysiological
constituents when the latter are part of a thinking being; the activities of societies on
thoseoftheirunitindividualswhentheseindividualsformpartoftheirsociety…Butit
contendsthattheconstituentsofeachgradeacquirenewproperties,newmodesofaction,
inbecomingpartofthe“emergent”thingof“higher”grade.Itholdsthatthephysics
ofatoms,ofmolecules,isnotfullyknowntillthesearestudiedinthelivingaswell
as in the non-living(1,2).
-Herbert Spencer Jennings, The Biological Basis of Human Nature, 1930
Noteworthy scientific advancements represent revisions to existing paradigms built from
repeatedfailureandignorance.Scientistsintentionallydevotethemselvestolivinginaworldofthe
unknown.Theythriveoffofthepursuitofknowledge.Thislifestyleinvolvesmuchfailuresinceno
experimentaldesigncanorshouldbeassumedaprioritoautomaticallyleadtosuccess.Sciencehas
beendescribedasaprocessofstumblingaroundinadarkroomuntilalightswitchisaccidentally
discovered,whichshedslightonthecurrenttopicofstudy.Oncethescientisthasmarveledatthis
newly lit room long enough to gain an appreciation for its décor, he or she then promptly moves
ontothenextdarkroom.Scientificadvancementisoftenpresentedinpopularcultureasinvolving
so-called“eureka”momentsofsingleindividuals,buttherealityisthatmajorinnovationisnearly
always the result of incremental modifications to existing models involving many individuals and
the tools accessible during a given era. That is not to say that major leaps in knowledge cannot
happen.However,itisnotalwaysguaranteedthatsuchideaswillremaininthepublicconsciousness
afterthedeathoftheinnovator.ConsidertheexampleofCharlesBabbage’sAnalyticalEngine,the
mechanical general-purpose computer first proposed in 1837. Though it was technically possible
tobuildusingthetechnologyofthetime,Babbage’sdesignwasneverconstructedduetothehigh
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