Abstract:
:The x-ray structure of LeuT, a bacterial homologue of Na(+)/Cl(-)-dependent neurotransmitter transporters, provides a great opportunity to better understand the molecular basis of monovalent cation selectivity in ion-coupled transporters. LeuT possesses two ion binding sites, NA1 and NA2, which are highly selective for Na(+). Extensive all-atom free-energy molecular dynamics simulations of LeuT embedded in an explicit membrane are performed at different temperatures and various occupancy states of the binding sites to dissect the molecular mechanism of ion selectivity. The results show that the two binding sites display robust selectivity for Na(+) over K(+) or Li(+), the competing ions of most similar radii. Of particular interest, the mechanism primarily responsible for selectivity for each of the two binding sites appears to be different. In NA1, selectivity for Na(+) over K(+) arises predominantly from the strong electrostatic field arising from the negatively charged carboxylate group of the leucine substrate coordinating the ion directly. In NA2, which comprises only neutral ligands, selectivity for Na(+) is enforced by the local structural restraints arising from the hydrogen-bonding network and the covalent connectivity of the polypeptide chain surrounding the ion according to a "snug-fit" mechanism.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Noskov SY,Roux Bdoi
10.1016/j.jmb.2008.01.015subject
Has Abstractpub_date
2008-03-28 00:00:00pages
804-18issue
3eissn
0022-2836issn
1089-8638pii
S0022-2836(08)00033-8journal_volume
377pub_type
杂志文章abstract::Members of the MarR family of winged helix transcriptional regulators have been shown to regulate multidrug and oxidative stress response, pathogenesis, and catabolism of aromatic compounds. Many respond to anionic lipophilic compounds in their capacity to bind DNA, and the co-crystal structure of MarR bound to salicy...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.05.027
更新日期:2005-07-22 00:00:00
abstract::The giant muscle protein titin (connectin) is known to serve as a cytoskeletal element in muscle sarcomeres. It elastically restrains lengthening sarcomeres, it aids the integrity and central positioning of the A-band in the sarcomere and it may act as a template upon which some sarcomeric components are laid down dur...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(02)00819-7
更新日期:2002-09-27 00:00:00
abstract::The structure of the yeast DNA-dependent RNA polymerase I (RNA Pol I), prepared by cryo-negative staining, was studied by electron microscopy. A structural model of the enzyme at a resolution of 1.8 nm was determined from the analysis of isolated molecules and showed an excellent fit with the atomic structure of the R...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(03)00510-2
更新日期:2003-06-20 00:00:00
abstract::L11 protein is located at the base of the L7/L12 stalk of the 50 S subunit of the Escherichia coli ribosome. Because of the flexible nature of the region, recent X-ray crystallographic studies of the 50 S subunit failed to locate the N-terminal domain of the protein. We have determined the position of the complete L11...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2001.4907
更新日期:2001-08-24 00:00:00
abstract::Centrin, an EF-hand calcium-binding protein, has been shown to be involved in the duplication of centrosomes, and Sfi1 (Suppressor of fermentation-induced loss of stress resistance protein 1) is one of its centrosomal targets. There are three isoforms of human centrin, but here we only considered centrin 2 (HsCen2). T...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2009.10.041
更新日期:2010-01-08 00:00:00
abstract::Wild-type hen lysozyme has been converted from its soluble native state into highly organized amyloid fibrils. In order to achieve this conversion, conditions were chosen to promote partial unfolding of the native globular fold and included heating of low-pH solutions and addition of organic solvents. Two peptides der...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2000.3862
更新日期:2000-07-14 00:00:00
abstract::Single crystals of cytochrome cd1 nitrite reductase from Thiosphaera pantotropha have been grown in the presence of ammonium sulphate by vapour diffusion techniques. Crystals are suitable for X-ray analysis and diffract to dmin = 1.5 A. They belong to space group P2(1) with unit cell dimensions of a = 107.8 A, b = 61....
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1993.1473
更新日期:1993-08-20 00:00:00
abstract::The presence of bound water in the solution structure of the IgG binding domain of streptococcal protein G has been investigated by nuclear magnetic resonance using three-dimensional 1H rotating frame Overhauser 1H-15N multiple quantum coherence spectroscopy. The backbone amide protons of three residues, Ala20, Gln32 ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(92)90247-h
更新日期:1992-02-20 00:00:00
abstract::Structural database-derived propensities for amino acids to adopt particular local protein structures, such as alpha-helix and beta-strand, have long been recognized and effectively exploited for the prediction of protein secondary structure. However, the experimental verification of database-derived propensities usin...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2007.07.059
更新日期:2007-10-26 00:00:00
abstract::The abundance of structural data available for retroviral proteases affords a unique opportunity to investigate structure activity relationships. Our approach attempts to genetically engineer an HIV (human immunodeficiency virus)-1 protease that is functionally equivalent to the HIV-2 and the SIV (simian immunodeficie...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1997.0891
更新日期:1997-04-04 00:00:00
abstract::The time-course of synthesis of long and short (abortive) transcripts by Escherichia coli RNA polymerase was investigated under single round conditions in vitro. The synthesis of long RNA initiated at the lambda PR (with an altered leader sequence) or at the lacUV5 promoter was completed within five minutes, but abort...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0100
更新日期:1996-03-01 00:00:00
abstract::The dependence of the electrophoretic mobility of small DNA rings on topological constraint was investigated in acrylamide or agarose gels as a function of DNA size (from approximately 350 to 1400 base-pairs), gel concentration and nucleotide sequence. Under appropriate adjustment between the size of the DNA and the g...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(86)90282-2
更新日期:1986-12-05 00:00:00
abstract::Protein folding is directed by the sequence of sidechains along the polypeptide backbone, but despite this the developement of sidechain interactions during folding is not well understood. Here, the thiol-active reagent, dithio-nitrobenzoic acid (DTNB), is used to probe the exposure of the cysteine sidechain thiols in...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.09.014
更新日期:2006-12-08 00:00:00
abstract::Aldo-keto reductases (AKRs) are a large superfamily of NADPH-dependent enzymes that catalyze the reduction of aldehydes, aldoses, dicarbonyls, steroids, and monosaccharides. While their precise physiological role is generally unknown, AKRs are nevertheless involved in the detoxification of a broad range of toxic metab...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2010.02.021
更新日期:2010-04-23 00:00:00
abstract::Analysis of the conformational differences between the oxy and deoxy forms of hemoglobin is complicated by shifting coordinate systems and correlated motions between different parts of the molecule. Methods independent of any frame of reference were used to study the differences in structure between the oxy and deoxy ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1997.1087
更新日期:1997-07-25 00:00:00
abstract::The crystal structure of malate dehydrogenase from Escherichia coli has been determined with a resulting R-factor of 0.187 for X-ray data from 8.0 to 1.87 A. Molecular replacement, using the partially refined structure of porcine mitochondrial malate dehydrogenase as a probe, provided initial phases. The structure of ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(92)90637-y
更新日期:1992-08-05 00:00:00
abstract::A variant of human growth hormone (hGH), in which 15 mutations were introduced with phage display mutagenesis to improve receptor binding affinity by 400-fold, yielded two related crystal forms diffracting to high resolution. The structure of this variant was determined in both crystal forms, one at 2.0 A resolution a...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1994.1135
更新日期:1994-02-11 00:00:00
abstract::We have identified Adrm1 as a novel component of the regulatory ATPase complex of the 26 S proteasome: Adrm1 was precipitated with an antibody to proteasomes and vice versa. Adrm1 co-migrated with proteasomes on gel-filtration chromatography and non-denaturing polyacrylamide gel electrophoresis. Adrm1 has been describ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.06.011
更新日期:2006-07-28 00:00:00
abstract::FSHD region gene 1 (FRG1) is a dynamic nuclear and cytoplasmic protein that, in skeletal muscle, shows additional localization to the sarcomere. Maintaining appropriate levels of FRG1 protein is critical for muscular and vascular development in vertebrates; however, its precise molecular function is unknown. This stud...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2011.06.014
更新日期:2011-08-12 00:00:00
abstract::Phospholamban physically interacts with the sarcoplasmic reticulum calcium pump (SERCA) and regulates contractility of the heart in response to adrenergic stimuli. We studied this interaction using electron microscopy of 2D crystals of SERCA in complex with phospholamban. In earlier studies, phospholamban oligomers we...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2010.11.014
更新日期:2011-01-21 00:00:00
abstract::A new affinity chromatographic procedure for the separation of transcriptionally active nucleosomes has been used to study the changes that take place in chromatin structure along the c-fos and c-myc genes when RNA synthesis is inhibited. Mercury-affinity chromatography separates the sulfhydryl-reactive nucleosomes of...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(90)90327-I
更新日期:1990-04-05 00:00:00
abstract::In order to study the effect of internal dynamics on the accuracy of NMR structures in detail, we generated NOE distance data from a long molecular dynamics trajectory of BPTI. Cross-relaxation rates were calculated from the trajectory by analysis of the appropriate proton-proton vector autocorrelation functions. A cr...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.2323
更新日期:1999-01-15 00:00:00
abstract::Pseudomonas aeruginosa is a priority pathogen for the development of new antibiotics, particularly because multi-drug-resistant strains of this bacterium cause serious nosocomial infections and are the leading cause of death in cystic fibrosis patients. Pyocins, bacteriocins of P. aeruginosa, are potent and diverse pr...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2020.04.020
更新日期:2020-06-12 00:00:00
abstract::Hsp90 is a highly conserved molecular chaperone that remodels hundreds of client proteins, many involved in the progression of cancer and other diseases. It functions with the Hsp70 chaperone and numerous cochaperones. The bacterial Hsp90 functions with an Hsp70 chaperone, DnaK, but is independent of Hsp90 cochaperone...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2015.10.010
更新日期:2015-12-04 00:00:00
abstract::A hallmark of the catalytically essential Walker B motif of P-loop NTPases is the presence of an acidic residue (aspartate/glutamate) for efficient Mg2+ coordination. Although the Walker B motif has been identified in well-studied examples of P-loop NTPases, its identity is ambiguous in many families, for example, in ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2020.07.024
更新日期:2020-09-18 00:00:00
abstract::We demonstrate that RecA protein-coated, short single-stranded DNA probes paired with a specific homologous DNA sequence in a linear duplex target molecule and accurately targeted the selected DNA sequence. RecA protein-coated complementary ssDNA probes were reacted with linear duplexes, and the homologously paired mo...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1993.1431
更新日期:1993-08-05 00:00:00
abstract::The clarification of the physico-chemical determinants underlying amyloid deposition is critical for our understanding of misfolding diseases. With this purpose we have performed a systematic all-atom molecular dynamics (MD) study of a series of single point mutants of the de novo designed amyloidogenic peptide STVIIE...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.03.081
更新日期:2005-06-10 00:00:00
abstract::The pre-steady-state kinetics of GTP hydrolysis catalysed by elongation factor G and ribosomes from Escherichia coli has been investigated by the method of quenched-flow. The GTPase activities either uncoupled from or coupled to the ribosomal translocation process were characterized under various experimental conditio...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(86)90495-x
更新日期:1986-06-20 00:00:00
abstract::The alcohol dehydrogenase (ADHase) enzyme catalyses the oxidation of alcohols to aldehydes or ketones using NAD+ as a cofactor. Functional ADHase from Drosophila lebanonensis is a dimer, with a monomeric molecular weight of 27,000 and with 254 residues in each polypeptide chain. Crystals of the protein have been grown...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(92)90705-o
更新日期:1992-09-05 00:00:00
abstract::The human kinetochore is a highly complex macromolecular structure that connects chromosomes to spindle microtubules (MTs) in order to facilitate accurate chromosome segregation. Centromere-associated protein E (CENP-E), a member of the kinesin superfamily, is an essential component of the kinetochore, since it is req...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2004.05.053
更新日期:2004-07-23 00:00:00