Journal Issue - Volume 16 Issue 9 (September 2007)
The structural and functional diversity of Hsp70 proteins from Plasmodium falciparum
- Addmore Shonhai, Aileen Boshoff, Gregory L. Blatch
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072918107 (p 1803-1818)
Abstract It is becoming increasingly apparent that heat shock proteins play an important role in the survival of Plasmodium falciparum against temperature changes associated with its passage from the cold‐blooded mosquito vector to the warm‐blooded human host. Interest in understanding the possible role of P. falciparum Hsp70s in the life cycle of the parasite has led to the identification of six HSP70 genes. Although most research attention has focused...
Docking and homology modeling explain inhibition of the human vesicular glutamate transporters
- Jonas Almqvist, Yafei Huang, Aatto Laaksonen, Da‐Neng Wang, Sven Hovmöller
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072944707 (p 1819-1829)
Abstract As membrane transporter proteins, VGLUT1–3 mediate the uptake of glutamate into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells. This function is crucial for exocytosis and the role of glutamate as the major excitatory neurotransmitter in the central nervous system. The three transporters, sharing 76% amino acid sequence identity in humans, are highly homologous but differ in regional expression...
Sm‐like protein Hfq: Location of the ATP‐binding site and the effect of ATP on Hfq–RNA complexes
- Veronique Arluison, Shravan K. Mutyam, Cameron Mura, Sergio Marco, Maxim V. Sukhodolets
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072883707 (p 1830-1841)
Abstract Sm‐like proteins are ubiquitous ring‐shaped oligomers that exhibit a variety of nucleic acid‐binding activities. They have been linked functionally to various cellular events involving RNA, and it is generally believed that their activity is exerted via the passive binding of nucleic acids. Our earlier studies of the Sm‐like Escherichia coli protein Hfq provided the first evidence indicating that Hfq is an ATP‐binding protein. Using a...
Probing the local conformational change of α 1 ‐antitrypsin
- Je‐Hyun Baek, Hana Im, Un‐Beom Kang, Ki Moon Seong, Cheolju Lee, Joon Kim, Myeong‐Hee Yu
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072911607 (p 1842-1850)
Abstract The native form of serpins (serine protease inhibitors) is a metastable conformation, which converts into a more stable form upon complex formation with a target protease. It has been suggested that movement of helix‐F (hF) and the following loop connecting to strand 3 of β‐sheet A (thFs3A) is critical for such conformational change. Despite many speculations inferred from analysis of the serpin structure itself, direct...
How similar are enzyme active site geometries derived from quantum mechanical theozymes to crystal structures of enzyme‐inhibitor complexes? Implications for enzyme design
- Jason DeChancie, Fernando R. Clemente, Adam J.T. Smith, Hakan Gunaydin, Yi‐Lei Zhao, Xiyun Zhang, K.N. Houk
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072963707 (p 1851-1866)
Abstract Quantum mechanical optimizations of theoretical enzymes (theozymes), which are predicted catalytic arrays of biological functionalities stabilizing a transition state, have been carried out for a set of nine diverse enzyme active sites. For each enzyme, the theozyme for the rate‐determining transition state plus the catalytic groups modeled by side‐chain mimics was optimized using B3LYP/6–31G(d) or, in one case, HF/3–21G(d)...
Patterns of protein–protein interactions in salt solutions and implications for protein crystallization
- André C. Dumetz, Ann M. Snellinger‐O'Brien, Eric W. Kaler, Abraham M. Lenhoff
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072957907 (p 1867-1877)
Abstract The second osmotic virial coefficients of seven proteins—ovalbumin, ribonuclease A, bovine serum albumin, α‐lactalbumin, myoglobin, cytochrome c, and catalase—were measured in salt solutions. Comparison of the interaction trends in terms of the dimensionless second virial coefficient b2 shows that, at low salt concentrations, protein–protein interactions can be either attractive or repulsive, possibly due to the anisotropy...
The structures of transcription factor CGL2947 from Corynebacterium glutamicum in two crystal forms: A novel homodimer assembling and the implication for effector‐binding mode
- Yong‐Gui Gao, Min Yao, Hiroshi Itou, Yong Zhou, Isao Tanaka
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072976907 (p 1878-1886)
Abstract Among the transcription factors, the helix‐turn‐helix (HTH) GntR family comprised of FadR, HutC, MocR, YtrA, AraR, and PlmA subfamilies regulates the most varied biological processes. Generally, proteins belonging to this family contain an N‐terminal DNA‐binding domain and a C‐terminal effector‐binding/oligomerization domain. The members of the YtrA subfamily are much shorter than other members of this family, with chain...
Amino‐acid interactions in psychrophiles, mesophiles, thermophiles, and hyperthermophiles: Insights from the quasi‐chemical approximation
- Richard A. Goldstein
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072947007 (p 1887-1895)
Abstract We investigate the mechanisms used by proteins to maintain thermostability throughout a wide range of temperatures. We use the quasi‐chemical approximation to estimate interaction strengths for psychrophiles, mesophiles, thermophiles, and hyperthermophiles. Our results highlight the importance of core packing in thermophilic stability. Although we observed an increase in the number of charged residues, the contribution of...
The crystal structure of M. leprae ML2640c defines a large family of putative S‐adenosylmethionine‐dependent methyltransferases in mycobacteria
- Martin Graña, Ahmed Haouz, Alejandro Buschiazzo, Isabelle Miras, Annemarie Wehenkel, Vincent Bondet, William Shepard, Francis Schaeffer, Stewart T. Cole, Pedro M. Alzari
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072982707 (p 1896-1904)
Abstract Mycobacterium leprae protein ML2640c belongs to a large family of conserved hypothetical proteins predominantly found in mycobacteria, some of them predicted as putative S‐adenosylmethionine (AdoMet)‐dependent methyltransferases (MTase). As part of a Structural Genomics initiative on conserved hypothetical proteins in pathogenic mycobacteria, we have determined the structure of ML2640c in two distinct crystal forms. As...
Constraining specificity in the N‐domain of tissue inhibitor of metalloproteinases‐1; gelatinase‐selective inhibitors
- Asmaa B. Hamze, Shuo Wei, Harinath Bahudhanapati, Smitha Kota, K. Ravi Acharya, Keith Brew
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072978507 (p 1905-1913)
Abstract The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs). Since unregulated MMP activities are linked to arthritis, cancer, and atherosclerosis, TIMP variants that are selective inhibitors of disease‐related MMPs have potential therapeutic value. The structures of TIMP/MMP complexes reveal that most interactions with the MMP involve the N‐terminal pentapeptide of...
Solution structure of Ca 2+ ‐free rat β‐parvalbumin (oncomodulin)
- Michael T. Henzl, John J. Tanner
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072837307 (p 1914-1926)
Abstract Relative to other parvalbumin isoforms, the mammalian β‐parvalbumin (oncomodulin) displays attenuated divalent ion affinity. High‐resolution structural data for the Ca2+‐bound protein have provided little insight into the physical basis for this behavior, prompting an examination of the unliganded state. This article describes the solution structure and peptide backbone dynamics of Ca2+‐free rat β‐parvalbumin (β‐PV). Ca2+ removal...
Theoretical study of the partial molar volume change associated with the pressure‐induced structural transition of ubiquitin
- Takashi Imai, Shusaku Ohyama, Andriy Kovalenko, Fumio Hirata
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072909007 (p 1927-1933)
Abstract The partial molar volume (PMV) change associated with the pressure‐induced structural transition of ubiquitin is analyzed by the three‐dimensional reference interaction site model (3D‐RISM) theory of molecular solvation. The theory predicts that the PMV decreases upon the structural transition, which is consistent with the experimental observation. The volume decomposition analysis demonstrates that the PMV reduction is...
Solution structure of recombinant somatomedin B domain from vitronectin produced in Pichia pastoris
- Magnus Kjaergaard, Henrik Gårdsvoll, Daniel Hirschberg, Steen Nielbo, Anand Mayasundari, Cynthia B. Peterson, Anna Jansson, Thomas J.D. Jørgensen, Flemming M. Poulsen, Michael Ploug
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072949607 (p 1934-1945)
Abstract The cysteine‐rich somatomedin B domain (SMB) of the matrix protein vitronectin is involved in several important biological processes. First, it stabilizes the active conformation of the plasminogen activator inhibitor (PAI‐1); second, it provides the recognition motif for cell adhesion via the cognate integrins (αvβ3, αvβ5, and αIIbβ3); and third, it binds the complex between urokinase‐type plasminogen activator (uPA) and its...
Branching in the sequential folding pathway of cytochrome c
- Mallela M.G. Krishna, Haripada Maity, Jon N. Rumbley, S. Walter Englander
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072922307 (p 1946-1956)
Abstract Previous results indicate that the folding pathways of cytochrome c and other proteins progressively build the target native protein in a predetermined stepwise manner by the sequential formation and association of native‐like foldon units. The present work used native state hydrogen exchange methods to investigate a structural anomaly in cytochrome c results that suggested the concerted folding of two segments that have little...
Destabilization of human glycine N‐methyltransferase by H176N mutation
- Zigmund Luka, Svetlana Pakhomova, Yury Luka, Marcia E. Newcomer, Conrad Wagner
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.072921507 (p 1957-1964)
Abstract In the presence of moderate (2–4 M) urea concentrations the tetrameric enzyme, glycine N‐methyltransferase (GNMT), dissociates into compact monomers. Higher concentrations of urea (7–8 M) promote complete denaturation of the enzyme. We report here that the H176N mutation in this enzyme, found in humans with hypermethioninaemia, significantly decreases stability of the tetramer, although H176 is located far from the...




