Abstract：
:As enzymes evolve and diverge from common ancestor sequences, they often keep their overall reaction chemistry but specialize in the binding of different cognate ligands. This study borrows methods for the computational assessment of 2D similarity of small molecules from the field of chemoinformatics, to examine the extent of structure conservation of cognate ligands binding to similar proteins. Proteins from 87 structural superfamilies from Escherichia coli form the core dataset, which is extended using homologues with functional assignments from any organism. We find that correlation of the substrate similarity with protein similarity (measured by either sequence-based or structure-based scores) can only be clearly established for very similar proteins. At low sequence identities, the superfamily to which a protein belongs can give helpful clues to its function, and more importantly, the confidence attached to such clues is superfamily-dependent. Our data indicate that only a few superfamilies show great substrate diversity, and that most exhibit conservation of at least part of the structural scaffold of the substrate.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Nobeli I,Spriggs RV,George RA,Thornton JMdoi
10.1016/j.jmb.2005.01.061keywords:
subject
Has Abstractpub_date
2005-03-25 00:00:00pages
415-36issue
2eissn
0022-2836issn
1089-8638pii
S0022-2836(05)00118-Xjournal_volume
347pub_type
杂志文章abstract：:The three-dimensional structure of the membrane glycoprotein neuraminidase of an escape mutant of the influenza virus strain A/Tokyo/3/67 has been determined to 3 A (1 A = 0.1 nm) resolution by X-ray diffraction. The mutant virus, selected by growing the virus in the presence of a monoclonal antibody to the neuraminid...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(88)90344-0
更新日期：1988-03-05 00:00:00
abstract：:The development of electrostatic interactions during the folding of the N-terminal domain of the ribosomal protein L9 (NTL9) is investigated by pH-dependent rate equilibrium free energy relationships. We show that Asp8, among six acidic residues, is involved in non-native, electrostatic interactions with K12 in the tr...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2006.04.038
更新日期：2006-06-23 00:00:00
abstract：:The thermodynamic hypothesis of Anfinsen postulates that structures and stabilities of globular proteins are determined by their amino acid sequences. Chain topology, however, is known to influence the folding reaction, in that motifs with a preponderance of local interactions typically fold more rapidly than those wi...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2010.03.001
更新日期：2010-04-30 00:00:00
abstract：:DNase I digestion of unlabelled chromatin has been used to determine the orientation of nucleosomes in the higher-order structure of chromatin. DNA digestion patterns were analysed quantitatively and compared with simulation curves that were generated with the experimentally obtained rate constants for cutting inside ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.1777
更新日期：1998-05-29 00:00:00
abstract：:Transient partial unfolding of proteins under native conditions may have significant consequences in the biochemical and biophysical properties of proteins. Native-state proteolysis offers a facile way to investigate the thermodynamic and kinetic accessibilities of partially unfolded forms (cleavable forms) under nati...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2009.08.006
更新日期：2009-10-23 00:00:00
abstract：:GDP liganded tubulin, which is inactive in microtubule assembly, polymerizes into rings more readily than the active GTP liganded protein. The structure of double rings made of highly purified GDP-tubulin has been characterized to 3 nm resolution with synchrotron X-ray solution scattering. The scattering profile has c...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1282
更新日期：1994-04-29 00:00:00
abstract：:The telomeric d(GGGGTT).d(AACCCC) repeat tracts (G4T2 repeats) in Tetrahymena thermophila macronuclei were shown previously to be packaged in a non-nucleosomal DNA-protein complex. Here, we demonstrate that these telomeric repeats, together with a short region of the immediately adjacent non-telomeric sequence, exist ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.1867
更新日期：1998-07-17 00:00:00
abstract：:We use flexible backbone protein design to explore the sequence and structure neighborhoods of naturally occurring proteins. The method samples sequence and structure space in the vicinity of a known sequence and structure by alternately optimizing the sequence for a fixed protein backbone using rotamer based sequence...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.11.062
更新日期：2005-02-18 00:00:00
abstract：:Kinetics of refolding of bovine carbonic anhydrase B have been studied by the "double-jump" technique (i.e. the dependence of protein refolding on delay time in the unfolded state after fast unfolding). It is shown that two stages (the slow with a relaxation time of t1/2 approximately equal to 120 s and the superslow ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/S0022-2836(05)80215-3
更新日期：1990-06-05 00:00:00
abstract：:The effect of GT/CA dinucleotide repeat tracts on RecA-dependent homologous recombination was examined in vitro. By measuring the binding of RecA protein to oligonucleotides containing GT or CA repeats using the surface plasmon resonance (BIAcore), we show that the efficiency of RecA protein binding is sequence depend...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1997.1293
更新日期：1997-10-17 00:00:00
abstract：:The nucleotide sequence of 6.2 kb (1 kb = 10(3) base-pairs) of DNA that encompasses the earliest replicating portion of the amplified dihydrofolate reductase domains of CHOC 400 cells has been determined. Origin region DNA contains two AluI family repeats, a novel repetitive element (termed ORR-1), a TGGGT-rich region...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(90)90008-A
更新日期：1990-01-05 00:00:00
abstract：:Characterization of the RNase P RNA gene derived from Borrelia burgdorferi reveals covariation of the conserved nucleotides at positions corresponding to nucleotides 128 and 230 in Escherichia coli RNase P RNA (M1 RNA). Single base substitutions at either of these positions in M1 RNA resulted in a lack of complementat...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1467
更新日期：1994-08-05 00:00:00
abstract：:The immI region of bacteriophage P1 includes the ant/reb gene, which encodes the antirepressor protein, and the c4 gene, which encodes a repressor molecule that negatively regulates antirepressor synthesis. The antirepressor interferes with the activity of the P1 repressor of lytic function, the product of the c1 gene...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(89)90591-3
更新日期：1989-10-20 00:00:00
abstract：:The second generation Hoechst-Bayer non-nucleoside inhibitor, HBY 097 (S-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3, 4-dihydroqui noxalin-2(1H)-thione), is an extremely potent inhibitor of HIV-1 reverse transcriptase (RT) and of HIV-1 infection in cell culture. HBY 097 selects for unusual drug-resistance mu...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.2171
更新日期：1998-11-27 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：:Like most cellular RNA enzymes, the bI5 group I intron requires binding by a protein cofactor to fold correctly. Here, we use single-molecule approaches to monitor the structural dynamics of the bI5 RNA in real time as it assembles with its CBP2 protein cofactor. These experiments show that CBP2 binds to the target RN...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2006.06.048
更新日期：2006-08-25 00:00:00
abstract：:Determining the critical structural features a ligand must possess in order to bind to its receptor is of key importance to the understanding of vital biological processes and to the rational design of small molecule therapeutics to modulate receptor function. We have developed a general strategy for determining such ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(03)00094-9
更新日期：2003-03-21 00:00:00
abstract：:The B-DNA decanucleotide C-G-A-T-C-G-6meA-T-C-G has been crystallized under the same conditions used earlier for C-G-A-T-C-G-A-T-C-G, but is found to adopt a new trigonal P3(2)21 packing mode instead of the expected orthorhombic P2(1)2(1)2(1) form. Unit cell dimensions a = b = 33.38 A, c = 98.30 A, gamma = 120 degrees...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1993.1325
更新日期：1993-06-05 00:00:00
abstract：:The solution structure of a DNA three-way junction (3H) containing two unpaired thymidine bases at the branch site (3HT2), was determined by NMR. Arms A and B of the 3HT2 form a quasi-continuous stacked helix, which is underwound at the junction and has an increased helical rise. The unstacked arm C forms an acute ang...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2000.4224
更新日期：2000-12-01 00:00:00
abstract：:Here we present the crystal structure of the Methanococcus jannaschii RelE-RelB (RelBE) toxin-antitoxin (TA) protein complex determined by the MIRAS (multiple isomorphous replacement with anomalous signal) method. The genes encoding this TA system are located in the chromosome of this archaeon and involved in stress r...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2009.08.048
更新日期：2009-11-06 00:00:00
abstract：:Enoyl-[acyl carrier protein] (ACP) reductase (ENR) is a key enzyme in type II fatty acid synthesis that catalyzes the last step in each elongation cycle. Therefore, it has been considered as a target for antibiotics. However, recent studies indicate that some pathogens have more than one ENR; in particular, Bacillus s...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2010.12.003
更新日期：2011-02-25 00:00:00
abstract：:The trimeric TolC protein of Escherichia coli comprises an outer membrane beta-barrel and a contiguous alpha-helical barrel projecting across the periplasm. This provides a single 140 A long pore for multidrug efflux and protein export. We have previously reported that trivalent cations such as hexammine cobalt can se...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.07.088
更新日期：2004-09-17 00:00:00
abstract：:We carry out a theoretical study of the vibrational and relaxation properties of naturally occurring proteins with the purpose of characterizing both the folding and equilibrium thermodynamics. By means of a suitable model, we provide a full characterization of the spectrum and eigenmodes of vibration at various tempe...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(02)00710-6
更新日期：2002-08-30 00:00:00
abstract：:Kinetic analysis of a mutant version of Escherichia coli aspartate transcarbamoylase in which Thr82 in the regulatory chain (Thr82r) was replaced by Ala results in a shift in the T <==> R equilibrium towards the T-state. In order to understand the structural determinants of this T-state stabilization, the X-ray struct...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.1923
更新日期：1998-08-07 00:00:00
abstract：:The U6 RNA internal stem-loop (U6 ISL) is a highly conserved domain of the spliceosome that is important for pre-mRNA splicing. The U6 ISL contains an internal loop that is in equilibrium between two conformations controlled by the protonation state of an adenine (pK(a)=6.5). Lower pH favors formation of a protonated ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2009.07.003
更新日期：2009-09-04 00:00:00
abstract：:Major histocompatibility complex (MHC) class I proteins are expressed on the cell surface where they present foreign and self-peptides to effector cells of the immune system. While an understanding of the structural prerequisites for antigen presentation has already been achieved, insight into subtype- or peptide-depe...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2011.11.021
更新日期：2012-01-13 00:00:00
abstract：:Toxin-antitoxin systems consist of a stable toxin, frequently with endonuclease activity, and a small, labile antitoxin, which sequesters the toxin into an inactive complex. Under unfavorable conditions, the antitoxin is degraded, leading to activation of the toxin and resulting in growth arrest, possibly also in bact...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2007.07.016
更新日期：2007-09-28 00:00:00
abstract：:Progress in the structure determination of bacteriorhodopsin, the protein component of purple membrane from Halobacterium halobium has been limited by the lack of three-dimensional phase information between 6 and 3 A resolution. By analogy with X-ray methods, it is possible that heavy-atom labelling of the membrane cr...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/S0022-2836(05)80214-1
更新日期：1990-06-05 00:00:00
abstract：:A monoclonal antibody (MF5), capable of recognizing a divalent cation-induced conformational change in myosin light chain 2 (LC2f), has been used to screen a cDNA library constructed in the expression vector lambda gt11. A clone has been isolated that contains the whole coding sequence of this myosin subunit. The ligh...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(85)90229-3
更新日期：1985-02-05 00:00:00
abstract：:Halobacterium salinarium is a chemo- and phototactic archaeon whose signal transduction pathway includes the classical two-component system made up of CheA and CheY. Deletion analysis of the che operon in H. salinarium has been undertaken. Following the removal of the entire operon, the importance of each of the four ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1996.0267
更新日期：1996-05-17 00:00:00
