Journal Issue - Volume 17 Issue 2 (February 2008)
The biochemistry and biology of extracellular plant lipid‐transfer proteins (LTPs)
- Trevor H. Yeats, Jocelyn K.C. Rose
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073300108 (p 191-198)
Abstract Plant lipid‐transfer proteins (LTPs) are abundant, small, lipid binding proteins that are capable of exchanging lipids between membranes in vitro. Despite their name, a role in intracellular lipid transport is considered unlikely, based on their extracellular localization. A number of other biological roles, including antimicrobial defense, signaling, and cell wall loosening, have been proposed, but conclusive evidence is...
Chemical shift assignment of the transmembrane helices of DsbB, a 20‐kDa integral membrane enzyme, by 3D magic‐angle spinning NMR spectroscopy
- Ying Li, Deborah A. Berthold, Robert B. Gennis, Chad M. Rienstra
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073225008 (p 199-204)
Abstract The Escherichia coli inner membrane enzyme DsbB catalyzes disulfide bond formation in periplasmic proteins, by transferring electrons to ubiquinone from DsbA, which in turn directly oxidizes cysteines in substrate proteins. We have previously shown that DsbB can be prepared in a state that gives highly resolved magic‐angle spinning (MAS) NMR spectra. Here we report sequential 13C and 15N chemical shift assignments for the majority of...
Solution NMR structure of the N‐terminal domain of the human DEK protein
- Matthew Devany, Ferdinand Kappes, Kuan‐Ming Chen, David M. Markovitz, Hiroshi Matsuo
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073244108 (p 205-215)
Abstract The human DEK protein has a long‐standing association with carcinogenesis since the DEK gene was originally identified in the t(6:9) chromosomal translocation in a subtype of patients with acute myelogenous leukemia (AML). Recent studies have partly unveiled DEK's cellular functions including apoptosis inhibition in primary cells as well as cancer cells, determination of 3′ splice site of transcribed RNA, and suppression of...
Electrostatic effects in unfolded staphylococcal nuclease
- Nicholas C. Fitzkee, Bertrand García‐Moreno E
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073081708 (p 216-227)
Abstract Structure‐based calculations of pKa values and electrostatic free energies of proteins assume that electrostatic effects in the unfolded state are negligible. In light of experimental evidence showing that this assumption is invalid for many proteins, and with increasing awareness that the unfolded state is more structured and compact than previously thought, a detailed examination of electrostatic effects in unfolded...
Structural determinants of nitroxide motion in spin‐labeled proteins: Solvent‐exposed sites in helix B of T4 lysozyme
- Zhefeng Guo, Duilio Cascio, Kálmán Hideg, Wayne L. Hubbell
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073174008 (p 228-239)
Abstract Site‐directed spin labeling provides a means for exploring structure and dynamics in proteins. To interpret the complex EPR spectra that often arise, it is necessary to characterize the rotamers of the spin‐labeled side chain and the interactions they make with the local environment in proteins of known structure. For this purpose, crystal structures have been determined for T4 lysozyme bearing a nitroxide side chain (R1)...
Involvement of DPP‐IV catalytic residues in enzyme–saxagliptin complex formation
- William J. Metzler, Joseph Yanchunas, Carolyn Weigelt, Kevin Kish, Herbert E. Klei, Dianlin Xie, Yaqun Zhang, Martin Corbett, James K. Tamura, Bin He, Lawrence G. Hamann, Mark S. Kirby, Jovita Marcinkeviciene
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073253208 (p 240-250)
Abstract The inhibition of DPP‐IV by saxagliptin has been proposed to occur through formation of a covalent but reversible complex. To evaluate further the mechanism of inhibition, we determined the X‐ray crystal structure of the DPP‐IV:saxagliptin complex. This structure reveals covalent attachment between S630 and the inhibitor nitrile carbon (C–O distance <1.3 Å). To investigate whether this serine addition is assisted by the...
Identification of phosphorylation sites in mammalian mitochondrial ribosomal protein DAP3
- Jennifer L. Miller, Hasan Koc, Emine C. Koc
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073185608 (p 251-260)
Abstract Mammalian mitochondrial ribosomes synthesize 13 proteins that are essential for oxidative phosphorylation. In addition to their role in protein synthesis, some of the mitochondrial ribosomal proteins have acquired functions in other cellular processes such as apoptosis. Death‐associated protein 3 (DAP3), also referred to as mitochondrial ribosomal protein S29 (MRP‐S29), is a GTP‐binding pro‐apoptotic protein located in the...
Critical contribution of VH–VL interaction to reshaping of an antibody: The case of humanization of anti‐lysozyme antibody, HyHEL‐10
- Takeshi Nakanishi, Kouhei Tsumoto, Akiko Yokota, Hidemasa Kondo, Izumi Kumagai
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073156708 (p 261-270)
Abstract To clarify the effects of humanizing a murine antibody on its specificity and affinity for its target, we examined the interaction between hen egg white lysozyme (HEL) and its antibody, HyHEL‐10 variable domain fragment (Fv). We selected a human antibody framework sequence with high homology, grafted sequences of six complementarity‐determining regions of murine HyHEL‐10 onto the framework, and investigated the interactions...
Estimating the length of transmembrane helices using Z‐coordinate predictions
- Costas Papaloukas, Erik Granseth, Håkan Viklund, Arne Elofsson
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073036108 (p 271-278)
Abstract Zpred2 is an improved version of ZPRED, a predictor for the Z‐coordinates of α‐helical membrane proteins, that is, the distance of the residues from the center of the membrane. Using principal component analysis and a set of neural networks, Zpred2 analyzes data extracted from the amino acid sequence, the predicted topology, and evolutionary profiles. Zpred2 achieves an average accuracy error of 2.18 Å (2.17 Å when an...
LTHREADER: Prediction of extracellular ligand–receptor interactions in cytokines using localized threading
- Vinay Pulim, Jadwiga Bienkowska, Bonnie Berger
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073178108 (p 279-292)
Abstract Identification of extracellular ligand–receptor interactions is important for drug design and the treatment of diseases. Difficulties in detecting these interactions using high‐throughput experimental techniques motivate the development of computational prediction methods. We propose a novel threading algorithm, LTHREADER, which generates accurate local sequence‐structure interface alignments and integrates various...
Buried water molecules in helical transmembrane proteins
- Robert Renthal
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073237508 (p 293-298)
Abstract Buried water molecules (having no contact with bulk solvent) in 30 helical transmembrane (TM) protein structures were identified. The average amount of buried water in helical TM proteins is about the same as for all water‐soluble (WS) proteins, but it is greater than the average for helical WS proteins. Buried waters in TM proteins make more polar contacts, and are more frequently found contacting helices than in WS...
Functional site profiling and electrostatic analysis of cysteines modifiable to cysteine sulfenic acid
- Freddie R. Salsbury, Stacy T. Knutson, Leslie B. Poole, Jacquelyn S. Fetrow
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073096508 (p 299-312)
Abstract Cysteine sulfenic acid (Cys‐SOH), a reversible modification, is a catalytic intermediate at enzyme active sites, a sensor for oxidative stress, a regulator of some transcription factors, and a redox‐signaling intermediate. This post‐translational modification is not random: specific features near the cysteine control its reactivity. To identify features responsible for the propensity of cysteines to be modified to sulfenic...
Structural characterization of partially folded intermediates of apomyoglobin H64F
- Stephan Schwarzinger, Ronaldo Mohana‐Borges, Gerard J.A. Kroon, H. Jane Dyson, Peter E. Wright
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073187208 (p 313-321)
Abstract We present a detailed investigation of unfolded and partially folded states of a mutant apomyoglobin (apoMb) where the distal histidine has been replaced by phenylalanine (H64F). Previous studies have shown that substitution of His64, located in the E helix of the native protein, stabilizes the equilibrium molten globule and native states and leads to an increase in folding rate and a change in the folding pathway. Analysis...
Unique fluorophores in the dimeric archaeal histones hMfB and hPyA1 reveal the impact of nonnative structure in a monomeric kinetic intermediate
- Matthew R. Stump, Lisa M. Gloss
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073224308 (p 322-332)
Abstract Homodimeric archaeal histones and heterodimeric eukaryotic histones share a conserved structure but fold through different kinetic mechanisms, with a correlation between faster folding/association rates and the population of kinetic intermediates. Wild‐type hMfB (from Methanothermus fervidus) has no intrinsic fluorophores; Met35, which is Tyr in hyperthermophilic archaeal histones such as hPyA1 (from Pyrococcus strain GB‐3A), was...
Enhanced performance in prediction of protein active sites with THEMATICS and support vector machines
- Wenxu Tong, Ronald J. Williams, Ying Wei, Leonel F. Murga, Jaeju Ko, Mary Jo Ondrechen
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073213608 (p 333-341)
Abstract Theoretical microscopic titration curves (THEMATICS) is a computational method for the identification of active sites in proteins through deviations in computed titration behavior of ionizable residues. While the sensitivity to catalytic sites is high, the previously reported sensitivity to catalytic residues was not as high, about 50%. Here THEMATICS is combined with support vector machines (SVM) to improve sensitivity for catalytic ...




