Journal Issue - Volume 18 Issue 1 (January 2009)
High tolerance to simultaneous active‐site mutations in TEM‐1 β‐lactamase: Distinct mutational paths provide more generalized β‐lactam recognition
- Pierre‐Yves De Wals, Nicolas Doucet, Joelle N. Pelletier
- Published in Wiley Interscience on Dec 02, 2008
- DOI: 10.1002/pro.25 (p 147-160)
Abstract The diversity in substrate recognition spectra exhibited by various β‐lactamases can result from one or a few mutations in the active‐site area. Using Escherichia coli TEM‐1 β‐lactamase as a template that efficiently hydrolyses penicillins, we performed site‐saturation mutagenesis simultaneously on two opposite faces of the active‐site cavity. Residues 104 and 105 as well as 238, 240, and 244 were targeted to verify their...
Single molecule effects of osteogenesis imperfecta mutations in tropocollagen protein domains
- Alfonso Gautieri, Simone Vesentini, Alberto Redaelli, Markus J. Buehler
- Published in Wiley Interscience on Dec 02, 2008
- DOI: 10.1002/pro.21 (p 161-168)
Abstract Osteogenesis imperfecta (OI) is a genetic disease characterized by fragile bones, skeletal deformities and, in severe cases, prenatal death that affects more than 1 in 10,000 individuals. Here we show by full atomistic simulation in explicit solvent that OI mutations have a significant influence on the mechanical properties of single tropocollagen molecules, and that the severity of different forms of OI is directly...
Ion‐specific modulation of protein interactions: Anion‐induced, reversible oligomerization of a fusion protein
- Yatin R. Gokarn, R. Matthew Fesinmeyer, Atul Saluja, Shawn Cao, Jane Dankberg, Andrew Goetze, Richard L. Remmele Jr., Linda O. Narhi, David N. Brems
- Published in Wiley Interscience on Dec 02, 2008
- DOI: 10.1002/pro.20 (p 169-179)
Abstract Ions can significantly modulate the solution interactions of proteins. We aim to demonstrate that the salt‐dependent reversible heptamerization of a fusion protein called peptibody A or PbA is governed by anion‐specific interactions with key arginyl and lysyl residues on its peptide arms. Peptibody A, an E. coli expressed, basic (pI = 8.8), homodimer (65.2 kDa), consisted of an IgG1‐Fc with two, C‐terminal peptide arms linked via...
OptGraft: A computational procedure for transferring a binding site onto an existing protein scaffold
- Hossein Fazelinia, Patrick C. Cirino, Costas D. Maranas
- Published in Wiley Interscience on Dec 02, 2008
- DOI: 10.1002/pro.2 (p 180-195)
Abstract One of the many challenging tasks of protein design is the introduction of a completely new function into an existing protein scaffold. In this study, we introduce a new computational procedure OptGraft for placing a novel binding pocket onto a protein structure so as its geometry is minimally perturbed. This is accomplished by introducing a two‐level procedure where we first identify where are the most appropriate...
Thiol‐disulfide organization in alliin lyase (alliinase) from garlic ( Allium sativum )
- Lev Weiner, Irina Shin, Linda J. W. Shimon, Talia Miron, Meir Wilchek, David Mirelman, Felix Frolow, Aharon Rabinkov
- Published in Wiley Interscience on Dec 02, 2008
- DOI: 10.1002/pro.10 (p 196-205)
Abstract Alliinase, an enzyme found in garlic, catalyzes the synthesis of the well‐known chemically and therapeutically active compound allicin (diallyl thiosulfinate). The enzyme is a homodimeric glycoprotein that belongs to the fold‐type I family of pyridoxal‐5′‐phosphate‐dependent enzymes. There are 10 cysteine residues per alliinase monomer, eight of which form four disulfide bridges and two are free thiols. Cys368 and Cys376...
High‐resolution NMR characterization of a spider‐silk mimetic composed of 15 tandem repeats and a CRGD motif
- Glendon D. McLachlan, Joseph Slocik, Robert Mantz, David Kaplan, Sean Cahill, Mark Girvin, Steve Greenbaum
- Published in Wiley Interscience on Dec 02, 2008
- DOI: 10.1002/pro.12 (p 206-216)
Abstract Multidimensional solution NMR spectroscopic techniques have been used to obtain atomic level information about a recombinant spider silk construct in hexafluoro‐isopropanol (HFIP). The synthetic 49 kDa silk‐like protein mimics authentic silk from Nephila clavipes, with the inclusion of an extracellular matrix recognition motif. 2D 1H‐15N HSQC NMR spectroscopy reveals 33 cross peaks, which were assigned to amino acid residues in the...
Using affinity chromatography to engineer and characterize pH‐dependent protein switches
- Martin Sagermann, Richard R. Chapleau, Elaine DeLorimier, Margarida Lei
- Published in Wiley Interscience on Dec 02, 2008
- DOI: 10.1002/pro.23 (p 217-228)
Abstract Conformational changes play important roles in the regulation of many enzymatic reactions. Specific motions of side chains, secondary structures, or entire protein domains facilitate the precise control of substrate selection, binding, and catalysis. Likewise, the engineering of allostery into proteins is envisioned to enable unprecedented control of chemical reactions and molecular assembly processes. We here study the...
RosettaHoles: Rapid assessment of protein core packing for structure prediction, refinement, design, and validation
- Will Sheffler, David Baker
- Published in Wiley Interscience on Dec 02, 2008
- DOI: 10.1002/pro.8 (p 229-239)
Abstract We present a novel method called RosettaHoles for visual and quantitative assessment of underpacking in the protein core. RosettaHoles generates a set of spherical cavity balls that fill the empty volume between atoms in the protein interior. For visualization, the cavity balls are aggregated into contiguous overlapping clusters and small cavities are discarded, leaving an uncluttered representation of the unfilled regions...
Structural modification of acyl carrier protein by butyryl group
- Bai‐Nan Wu, Yong‐Mei Zhang, Charles O. Rock, Jie J. Zheng
- Published in Wiley Interscience on Dec 02, 2008
- DOI: 10.1002/pro.11 (p 240-246)
Abstract Fatty acid synthesis in bacteria is catalyzed by a set of individual enzymes known as the type II fatty acid synthase. Acyl carrier protein (ACP) shuttles the acyl intermediates between individual pathway enzymes. In this study, we determined the solution structures of three different forms of ACP, apo‐ACP, ACP, and butyryl‐ACP under identical experimental conditions. The structural studies revealed that attachment of...
A summary of the measured p K values of the ionizable groups in folded proteins
- Gerald R. Grimsley, J. Martin Scholtz, C. Nick Pace
- Published in Wiley Interscience on Dec 02, 2008
- DOI: 10.1002/pro.19 (p 247-251)
Abstract We tabulated 541 measured pK values reported in the literature for the Asp, Glu, His, Cys, Tyr, and Lys side chains, and the C and N termini of 78 folded proteins. The majority of these values are for the Asp, Glu, and His side chains. The average pK values are Asp 3.5 ± 1.2 (139); Glu 4.2 ± 0.9 (153); His 6.6 ± 1.0 (131); Cys 6.8 ± 2.7 (25); Tyr 10.3 ± 1.2 (20); Lys 10.5 ± 1.1 (35); C‐terminus 3.3 ± 0.8 (22) and N‐terminus 7.7 ± 0.5...
Mechanical unfolding of covalently linked GroES: Evidence of structural subunit intermediates
- Isao Sakane, Kunihiro Hongo, Tomohiro Mizobata, Yasushi Kawata
- Published in Wiley Interscience on Dec 02, 2008
- DOI: 10.1002/pro.7 (p 252-257)
Abstract It is difficult to determine the structural stability of the individual subunits or protomers of many proteins in the cell that exist in an oligomeric or complexed state. In this study, we used single‐molecule force spectroscopy on seven subunits of covalently linked cochaperonin GroES (ESC7) to evaluate the structural stability of the subunit. A modified form of ESC7 was immobilized on a mica surface. The force‐extension...




