Abstract:
:The increasing number and diversity of protein sequence families requires new methods to define and predict details regarding function. Here, we present a method for analysis and prediction of functional sub-types from multiple protein sequence alignments. Given an alignment and set of proteins grouped into sub-types according to some definition of function, such as enzymatic specificity, the method identifies positions that are indicative of functional differences by comparison of sub-type specific sequence profiles, and analysis of positional entropy in the alignment. Alignment positions with significantly high positional relative entropy correlate with those known to be involved in defining sub-types for nucleotidyl cyclases, protein kinases, lactate/malate dehydrogenases and trypsin-like serine proteases. We highlight new positions for these proteins that suggest additional experiments to elucidate the basis of specificity. The method is also able to predict sub-type for unclassified sequences. We assess several variations on a prediction method, and compare them to simple sequence comparisons. For assessment, we remove close homologues to the sequence for which a prediction is to be made (by a sequence identity above a threshold). This simulates situations where a protein is known to belong to a protein family, but is not a close relative of another protein of known sub-type. Considering the four families above, and a sequence identity threshold of 30 %, our best method gives an accuracy of 96 % compared to 80 % obtained for sequence similarity and 74 % for BLAST. We describe the derivation of a set of sub-type groupings derived from an automated parsing of alignments from PFAM and the SWISSPROT database, and use this to perform a large-scale assessment. The best method gives an average accuracy of 94 % compared to 68 % for sequence similarity and 79 % for BLAST. We discuss implications for experimental design, genome annotation and the prediction of protein function and protein intra-residue distances.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Hannenhalli SS,Russell RBdoi
10.1006/jmbi.2000.4036keywords:
subject
Has Abstractpub_date
2000-10-13 00:00:00pages
61-76issue
1eissn
0022-2836issn
1089-8638pii
S0022-2836(00)94036-1journal_volume
303pub_type
杂志文章abstract::The acid and base catalytic rate constants, kH, obs and kOH, obs and the pH at the minimum rate, pHmin, of 25 rapidly exchanging protons in bovine pancreatic trypsin inhibitor have been determined. Here we report the labeling procedure giving 1H nuclear magnetic resonance spectral resolution of seven additional rapidl...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(87)90359-7
更新日期:1987-02-20 00:00:00
abstract::Methods for the prediction of protein function from structure are of growing importance in the age of structural genomics. Here, we focus on the problem of identifying sites of potential serine protease inhibitor interactions on the surface of proteins of known structure. Given that there is no sequence conservation w...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1999.3389
更新日期:2000-02-18 00:00:00
abstract::We have developed a procedure in which disulfide cross-links are used to identify regions of proteins that undergo functionally important intramolecular motion. The approach was applied to the identification of disulfide bonds that stabilize the active state of the yeast α-mating pheromone receptor Ste2p, a member of ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2012.02.024
更新日期:2012-05-18 00:00:00
abstract::A novel gene from the nematode Caenorhabditis elegans was isolated by hybridization with a human calmodulin complementary DNA probe. This gene, cal-1, is present at one copy per haploid genome. In-situ hybridization of the cloned gene to metaphase chromosomes allowed us to assign it to the nematode linkage group IV. T...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(86)90002-1
更新日期:1986-08-05 00:00:00
abstract::Carbon catabolite repression (CCR) of several operons in Bacillus subtilis and Bacillus megaterium is mediated by the cis-acting cre sequence and trans-acting catabolite control protein (CcpA). We describe purification of CcpA from B. megaterium and its interaction with regulatory sequences from the xyl operon. Specif...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0820
更新日期:1997-03-07 00:00:00
abstract::FUGUE, a program for recognizing distant homologues by sequence-structure comparison (http://www-cryst.bioc.cam.ac.uk/fugue/), has three key features. (1) Improved environment-specific substitution tables. Substitutions of an amino acid in a protein structure are constrained by its local structural environment, which ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2001.4762
更新日期:2001-06-29 00:00:00
abstract::Based on sequence and phylogenetic analyses, glycoside hydrolase (GH) family 3 can be divided into several clusters that differ in the length of their primary sequences. However, structural data on representatives of GH3 are still scarce, since only three of their structures are known and only one of them has been tho...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2010.01.072
更新日期:2010-04-02 00:00:00
abstract::Interaction of the leader RNA with the unphosphorylated P-protein has been proposed to play a key role in the transcription-replication transition of Chandipura virus, a model rhabdovirus. Electrophoretic mobility shift assay with the leader RNA and the unphosphorylated P-protein demonstrated existence of two distinct...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2004.03.081
更新日期:2004-06-18 00:00:00
abstract::The three-dimensional solution structure of circulin A, a 30 residue polypeptide from the African plant Chassalia parvifolia, has been determined using two-dimensional 1H-NMR spectroscopy. Circulin A was originally identified based upon its inhibition of the cytopathic effects and replication of the human immunodefici...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.2276
更新日期:1999-01-08 00:00:00
abstract::Fibrin formation from fibrinogen is a rare process in the healthy organism but is a pathological feature of thrombotic events, cancer and a wide range of inflammatory conditions. We have designed and constructed an antibody phage display library (containing 13 billion clones) for the selective recognition of the N-ter...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2014.07.023
更新日期:2014-10-23 00:00:00
abstract::The protection of telomeres 1 (Pot1) proteins specifically recognize the single-stranded 3' end of the telomere, an activity essential for sustained cellular viability and proliferation. The current model for the telomeric single-stranded DNA (ssDNA) binding activity of Schizosaccharomyces pombe Pot1 is based on a 20 ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.06.002
更新日期:2006-08-04 00:00:00
abstract::The ribosomal protein L30 from yeast Saccharomyces cerevisiae auto-regulates its own synthesis by binding to a structural element in both its pre-mRNA and its mRNA. The three-dimensional structures of L30 in the free (f L30) and the pre-mRNA bound (b L30) forms have been solved by nuclear magnetic resonance spectrosco...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1999.3044
更新日期:1999-09-17 00:00:00
abstract::The late genes of bacteriophage P2 are clustered into four transcription units. We have reported the transcription initiation sites for two of the late messenger RNAs, encoding genes QP and ONMLKRS. We have now located the 5' ends of the two remaining late mRNAs. The first gene in the VJHG transcription unit has been ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(85)90226-8
更新日期:1985-02-05 00:00:00
abstract::Interactions of polymerase X from African swine fever virus with single-stranded DNA (ssDNA) have been studied, using quantitative fluorescence titration and analytical ultracentrifugation techniques. Experiments were performed with a fluorescent etheno-derivative of ssDNA oligomers. Studies of unmodified ssDNA oligom...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.10.061
更新日期:2006-02-10 00:00:00
abstract::Protic ionic liquids (PILs) are currently being shown to be as interesting and valuable to chemical manipulations as the well-known aprotic ionic liquids (APIL). PILs have the additional advantage that the proton activity (PA) can be adjusted by the choice of Bronsted base and Bronsted acid used in their formation. In...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2008.02.050
更新日期:2008-05-02 00:00:00
abstract::Mimivirus is the largest known virus. Using cryo-electron microscopy, the virus was shown to be icosahedral, covered by long fibers, and appears to have at least two lipid membranes within its protein capsid. A unique vertex, presumably for attachment and infection of the host, can be seen for particles that have a su...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.08.060
更新日期:2005-10-28 00:00:00
abstract::We have developed a procedure to predict the peptide binding specificity of an SH3 domain from its sequence. The procedure utilizes information extracted from position-specific contacts derived from six SH3/peptide or SH3/protein complexes of known structure. The framework of SH3/peptide contacts defined on the struct...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2000.3670
更新日期:2000-04-28 00:00:00
abstract::Interferons (IFN) are multi-functional proteins that induce a large number of genes which mediate many biological processes including host defense, cell growth control, signaling, and metabolism. Bioinformatics analysis of the 3'-untranslated regions of IFN-stimulated genes (ISGs) showed that the AU-rich elements (ARE...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2004.07.065
更新日期:2004-09-17 00:00:00
abstract::The use of carbohydrate-mimicking peptides to induce immune responses against surface polysaccharides of pathogenic bacteria offers a novel approach to vaccine development. Factors governing antigenic and immunogenic mimicry, however, are complex and poorly understood. We have addressed this question using the anti-li...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2009.03.057
更新日期:2009-05-15 00:00:00
abstract::In eukaryotes, cellular levels of adenosine monophosphate (AMP) signal the metabolic state of the cell. AMP concentrations increase significantly upon metabolic stress, such as glucose deprivation in yeast. Here, we show that several DEAD-box RNA helicases are sensitive to AMP, which is not produced during ATP hydroly...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2013.05.006
更新日期:2013-10-23 00:00:00
abstract::6,7-Dimethyl-8-ribityllumazine synthase (lumazine synthase) catalyses the penultimate step in the biosynthesis of riboflavin. In Bacillus subtilis, 60 lumazine synthase subunits form an icosahedral capsid enclosing a homotrimeric riboflavin synthase unit. The ribH gene specifying the lumazine synthase subunit can be e...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(02)01473-0
更新日期:2003-02-21 00:00:00
abstract::Two crystal forms of hydroxypyruvate reductase (D-glycerate dehydrogenase) from the methylotrophic bacterium Hyphomicrobium methylovorum have been grown from ammonium sulphate solutions. One crystal form is triclinic, with unit cell parameters a = 60.4 A, b = 60.5 A, c = 66.3 A, alpha = 102.3 degrees, beta = 113.7 deg...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(92)90410-l
更新日期:1992-06-05 00:00:00
abstract::Interactions of rat DNA polymerase beta with a single-stranded (ss) DNA have been studied using the quantitative fluorescence titration technique. Examination of the fluorescence changes accompanying the binding, as a function of the thermodynamically rigorous binding density of rat pol beta-ssDNA complexes, reveals t...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.2252
更新日期:1998-12-11 00:00:00
abstract::An algorithm is developed for the analysis of the X-ray scattering spectra of lamellar systems, by reference to a precise physical model. The model consists of identical planar lamellae (the motif), all parallel and stacked in a one-dimensional crystal with four types of defect: stacking disorder, finite size of the c...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(05)80358-4
更新日期:1990-10-05 00:00:00
abstract::Vascular endothelial (VE) cadherin is the surface glycoprotein cadherin specific to the endothelium that mediates cell-cell adhesion and plays a major role in the remodeling, gating, and maturation of vascular vessels. To investigate the contribution of individual VE-cadherins to endothelial cell-cell interactions and...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.02.021
更新日期:2006-05-05 00:00:00
abstract::A protein fragment from the Tec family member Rlk (also known as Txk) containing a single proline-rich ligand adjacent to a Src homology 3 (SH3) domain has been investigated by nuclear magnetic resonance (NMR) spectroscopy. Analysis of the concentration dependence of the chemical shifts, NMR linewidths and self-diffus...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(03)00531-x
更新日期:2003-06-20 00:00:00
abstract::Subtilisin E is synthesized in Bacillus subtilis as a preprosubtilisin. The prepeptide is removed by a signal peptidase, and the propeptide is cleaved from the mature protein by the catalytic domain of subtilisin itself in an autocatalytic fashion. A six residue histidine-tag was attached to the C terminus of prosubti...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0538
更新日期:1996-10-11 00:00:00
abstract::The effects of RNA methylation on HIV-1 replication remain largely unknown. Recent studies have discovered new insights into the effect of 2'-O-methylation and 5-methylcytidine marks on the HIV-1 RNA genome. As so far, HIV-1 benefits from diverse RNA methylations through distinct mechanisms. In this review, we summari...
journal_title:Journal of molecular biology
pub_type: 杂志文章,评审
doi:10.1016/j.jmb.2019.09.021
更新日期:2019-12-06 00:00:00
abstract::Aminoacyl-tRNA synthetases are validated molecular targets for anti-infective drug discovery because of their essentiality in protein synthesis. Thanks to genome sequencing, it is now possible to systematically study aminoacyl-tRNA synthetases from human eukaryotic parasites as putative targets for novel drug discover...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2010.11.049
更新日期:2011-01-28 00:00:00
abstract::The Escherichia coli dnaA gene is required for replication of the bacterial chromosome. To identify residues critical for its replication activity, a method to select novel mutations was developed that relied on lytic growth of lambda from an inserted pSC101 replication origin. Replication from the lambda origin was i...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1997.1209
更新日期:1997-09-05 00:00:00