Double-mutant cycles: a powerful tool for analyzing protein structure and function

A Horovitz - Folding and Design, 1996 - cell.com
A double-mutant cycle involves wild-type protein, two single mutants and the corresponding
double mutant protein. If the change in free energy associated with a structural or functional …

Tunneling and dynamics in enzymatic hydride transfer

ZD Nagel, JP Klinman - Chemical reviews, 2006 - ACS Publications
Enzymes continue to be the subject of intensive research efforts because of their ability to
accelerate chemical reactions by factors as large as 1020 with extraordinary selectivity. 1 …

[HTML][HTML] Recognition of the polyubiquitin proteolytic signal

JS Thrower, L Hoffman, M Rechsteiner… - The EMBO journal, 2000 - embopress.org
Polyubiquitin chains linked through Lys48 are the principal signal for targeting substrates to
the 26S proteasome. Through studies of structurally defined, polyubiquitylated model …

Network of coupled promoting motions in enzyme catalysis

PK Agarwal, SR Billeter… - Proceedings of the …, 2002 - National Acad Sciences
A network of coupled promoting motions in the enzyme dihydrofolate reductase is identified
and characterized. The present identification is based on genomic analysis for sequence …

Creation of drug-specific herpes simplex virus type 1 thymidine kinase mutants for gene therapy.

ME Black, TG Newcomb… - Proceedings of the …, 1996 - National Acad Sciences
Herpes simplex virus type 1 (HSV-1) thymidine kinase is currently used as a suicide agent in
the gene therapy of cancer. This therapy is based on the preferential phosphorylation of …

Structures and mechanisms of Nudix hydrolases

AS Mildvan, Z Xia, HF Azurmendi, V Saraswat… - Archives of biochemistry …, 2005 - Elsevier
Nudix hydrolases catalyze the hydrolysis of nucleoside diphosphates linked to other
moieties, X, and contain the sequence motif or Nudix box, GX5EX7REUXEEXGU. The …

Challenges in enzyme mechanism and energetics

DA Kraut, KS Carroll, D Herschlag - Annual review of …, 2003 - annualreviews.org
▪ Abstract Since the discovery of enzymes as biological catalysts, study of their enormous
catalytic power and exquisite specificity has been central to biochemistry. Nevertheless …

The importance of additive and non-additive mutational effects in protein engineering.

MT Reetz - Angewandte Chemie International Edition, 2013 - search.ebscohost.com
Additive or non‐additive, that is the question: The increasing awareness of non‐additive
cooperative mutational effects in protein engineering is currently providing new theoretical …

Mechanisms of signaling and related enzymes

AS Mildvan - Proteins: Structure, Function, and Bioinformatics, 1997 - Wiley Online Library
Most enzymes involved in cell signaling, such as protein kinases, protein phosphatases,
GTPases, and nucleotide cyclases catalyze nucleophilic substitutions at phosphorus. When …

Coupling interactions of distal residues enhance dihydrofolate reductase catalysis: mutational effects on hydride transfer rates

PTR Rajagopalan, S Lutz, SJ Benkovic - Biochemistry, 2002 - ACS Publications
Recently, the participation in catalysis of residues spatially removed from the enzyme's
active site has received considerable attention. The influence of the distal Gly-121 residue …