Journal Issue - Volume 6 Issue 5 (May 1997)
Interleukin‐6: Structure‐function relationships
- Richard J. Simpson, Annet Hammacher, David K. Smith, Jacqueline M. Matthews, Larry D. Ward
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060501 (p 929-955)
Abstract Interleukin‐6 (IL‐6) is a multifunctional cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities and its potent ability to induce the acute phase response. Overexpression of IL‐6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post‐menopausal osteoporosis. Hence,...
Homology modeling using simulated annealing of restrained molecular dynamics and conformational search calculations with CONGEN: Application in predicting the three‐dimensional structure of murine homeodomain Msx‐1
- Haicheng Li, Roberto Tejero, Daniel Monleon, Donna Bassolino‐Klimas, Cory Abate‐Shen, Robert E. Bruccoleri, Gaetano T. Montelione
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060502 (p 956-970)
Abstract We have developed an automatic approach for homology modeling using restrained molecular dynamics and simulated annealing procedures, together with conformational search algorithms available in the molecular mechanics program CONGEN (Bruccoleri RE, Karplus M, 1987, Biopolymers 26:137–168). The accuracy of the method is validated by “predicting” structures of two homeodomain proteins with known three‐dimensional structures,...
Characterization of the allosteric binding pocket of human liver fructose‐1,6‐bisphosphatase by protein crystallography and inhibitor activity studies
- L. F. Iversen, M. Brzozowski, S. Hastrup, R. Hubbard, J. S. Kastrup, I. K. Larsen, L. Nærum, L. Nørskov‐Lauridsen, P. B. Rasmussen, L. Thim, F. C. Wiberg, K. Lundgren
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060503 (p 971-982)
Abstract The structures of three complexes of human fructose‐1,6‐bisphosphatase (FB) with the allosteric inhibitor AMP and two AMP analogues have been determined and all fully refined. The data used for structure determination were collected at cryogenic temperature (110 K), and with the use of synchrotron radiation. The structures reveal a common mode of binding for AMP and formycine monophosphate (FMP)....
Predicted structure of the extracellular region of ligand‐gated ion‐channel receptors shows SH2‐like and SH3‐like domains forming the ligand‐binding site
- Jill E. Gready, Shoba Ranganathan, Peter R. Schofield, Yo Matsuo, Ken Nishikawa
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060504 (p 983-998)
Abstract Fast synaptic neurotransmission is mediated by ligand‐gated ion‐channel (LGIC) receptors, which include receptors for acetylcholine, serotonin, GABA, glycine, and glutamate. LGICs are pentamers with extracellular ligand‐binding domains and form integral membrane ion channels that are selective for cations (acetylcholine and serotonin 5HT3 receptors) or anions (GABAA and glycine receptors and the invertebrate glutamate‐binding chloride...
Template‐based docking of a prolactin receptor proline‐rich motif octapeptide to FKBP12: Implications for cytokine receptor signaling
- K. V. Soman, B. A. Hanks, H. Tien, M. V. Chari, K. D. O'Neal, J. D. Morrisett
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060505 (p 999-1008)
Abstract A conserved proline‐rich motif (PRM) in the cytoplasmic domain of cytokine receptors has been suggested to be a signaling switch regulated by the action of the FK506 binding protein (FKBP) family of peptidylprolyl isomerases (O'Neal KD, Yu‐Lee LY, Shearer WT, 1995, Ann NY Acad Sci 766:282–284). We have docked the prolactin receptor PRM (Ile1‐Phe2‐Pro3‐Pro4‐Val5‐Pro6‐Gly7‐Pro8) to the ligand binding site of FKBP12. The procedure...
Three‐dimensional structures of glycolate oxidase with bound active‐site inhibitors
- Kaj Stenberg, Ylva Lindqvist
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060506 (p 1009-1015)
Abstract A key step in plant photorespiration, the oxidation of glycolate to glyoxylate, is carried out by the peroxisomal flavoprotein glycolate oxidase (EC 1.1.3.15). The three‐dimensional structure of this α/β barrel protein has been refined to 2 Å resolution (Lindqvist Y. 1989. J Mol Biol 209:151‐166). FMN dependent glycolate oxidase is a member of the family of α‐hydroxy acid oxidases. Here we describe the crystallization and...
Identification of a novel bond between a histidine and the essential tyrosine in catalase HPII of Escherichia coli
- Jeronimo Bravo, Ignacio Fita, Juan C. Ferrer, Werner Ens, Alex Hillar, Jacek Switala, Peter C. Loewen
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060507 (p 1016-1023)
Abstract A bond between the Nδ of the imidazole ring of His 392 and the Cβ of the essential Tyr 415 has been found in the refined crystal structure at 1.9 Å resolution of catalase HPII of Escherichia coli. This novel type of covalent linkage is clearly defined in the electron density map of HPII and is confirmed by matrix‐assisted laser desorption/ionization mass spectrometry analysis of tryptic digest mixtures. The geometry of the bond is compatible ...
Solvation effects are responsible for the reduced inhibitor affinity of some HIV‐1 PR mutants
- Fredy Sussman, M. Carmen Villaverde, Alan Davis
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060508 (p 1024-1030)
Abstract The formulation of HIV‐1 PR inhibitors as anti‐viral drugs has been hindered by the appearance of protease strains that present drug resistance to these compounds. The mechanism by which the HIV‐1 PR mutants lower their affinity for the inhibitor is not yet fully understood. We have applied a modified Poisson‐Boltzmann method to the evaluation of the molecular interactions that contribute to the lowering of the inhibitor...
The role of divalent cations in structure and function of murine adenosine deaminase
- Bruce F. Cooper, Vera Sideraki, David K. Wilson, David Y. Dominguez, Sandra W. Clark, Florante A. Quiocho, Frederick B. Rudolph
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060509 (p 1031-1037)
Abstract For murine adenosine deaminase, we have determined that a single zinc or cobalt cofactor bound in a high affinity site is required for catalytic function while metal ions bound at an additional site(s) inhibit the enzyme. A catalytically inactive apoenzyme of murine adenosine deaminase was produced by dialysis in the presence of specific zinc chelators in an acidic buffer. This represents the first production of the...
Design, synthesis, expression, and characterization of the genes for mouse FcγRIIb1 and FcγRIIb2 cytoplasmic regions
- Lixin Chen, Nancy L. Thompson, Gary J. Pielak
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060510 (p 1038-1046)
Abstract The cytoplasmic regions of the mouse low‐affinity FcγRII isoforms, mFcγRIIb1, and mFcγRIIb2, play a key role in signal transduction by mediating different cellular functions. mFcγRIIb1 has a 94‐residue cytoplasmic region, whereas mFcγRIIb2 has a 47‐residue cytoplasmic region. Genes encoding the cytoplasmic regions of mFcγRIIb1 (b1‐94) and mFcγRIIb2 (b2‐47) were designed, synthesized, and expressed as fusion proteins in...
Hsc66 and Hsc20, a new heat shock cognate molecular chaperone system from Escherichia coli
- Larry E. Vickery, Jonathan J. Silberg, Dennis T. Ta
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060511 (p 1047-1056)
Abstract The hscA and hscB genes of Escherichia coli encode novel chaperone and co‐chaperone proteins, designated Hsc66 and Hsc20, respectively. We have overproduced and purified Hsc66 and Hsc20 in high yield in E. coli and describe their initial characterization including absorbance, fluorescence, and circular dichroism spectra. Immunoblot analyses of E. coli cultures using antisera to Hsc66 and Hsc20 raised in rabbits establish that Hsc66 and...
Consistency in structural energetics of protein folding and peptide recognition
- Chao Zhang, James L. Cornette, Charles Delisi
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060512 (p 1057-1064)
Abstract We report a new free energy decomposition that includes structure‐derived atomic contact energies for the desolvation component, and show that it applies equally well to the analysis of single‐domain protein folding and to the binding of flexible peptides to proteins. Specifically, we selected the 17 single‐domain proteins for which the three‐dimensional structures and thermodynamic unfolding free energies are available. By...
Hexafluoroacetone hydrate as a structure modifier in proteins: Characterization of a molten globule state of hen egg‐white lysozyme
- Surajit Bhattacharjya, Padmanabhan Balaram
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060513 (p 1065-1073)
Abstract A molten globule‐like state of hen egg‐white lysozyme has been characterized in 25% aqueous hexafluoroacetone hydrate (HFA) by CD, fluorescence, NMR, and H/D exchange experiments. The far UV CD spectra of lysozyme in 25% HFA supports retention of native‐like secondary structure while the loss of near UV CD bands are indicative of the overall collapse of the tertiary structure. The intermediate state in 25% HFA exhibits an...
Cysteine reactivity in Thermoanaerobacter brockii alcohol dehydrogenase
- Moshe Peretz, Lev M. Weiner, Yigal Burstein
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060514 (p 1074-1083)
Abstract The free cysteine residues in the extremely thermophilic Thermoanaerobacter brockii alcohol dehydrogenase (TBADH) were characterized using selective chemical modification with the stable nitroxyl biradical bis(1‐oxy‐2,2,5,5‐tetramethyl‐3‐imidazoline‐4‐yl)disulfide, via a thiol‐disulfide exchange reaction and with 2[14C]iodoacetic acid, via S‐alkylation. The respective reactions were monitored by electron paramagnetic resonance (EPR) and ...
Energy profile of maltooligosaccharide permeation through maltoporin as derived from the structure and from a statistical analysis of saccharide‐protein interactions
- Joachim E. W. Meyer, Georg E. Schulz
- Published in Wiley Interscience on Dec 31, 2008
- DOI: 10.1002/pro.5560060515 (p 1084-1091)
Abstract The crystal structure of the maltodextrin‐specific porin from Salmonella typhimurium ligated with a maltotrioside at the pore eyelet is known at 2.4 Å resolution. The three glucose units assume a conformation close to the natural amylose helix. The pore eyelet fits exactly the cross‐section of a maltooligosaccharide chain and thus functions as a constraining orifice. The oligomer permeates the membrane by screwing along the amylose...




