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 ligand binding motifs using low temperature NMR structures of peptides with the desired receptor binding properties. This approach has been successfully applied to determine a binding motif for the chemokine receptor CXCR4. The motif identified provides a detailed guide for the design of small molecule antagonists against CXCR4, which are much sought after to aid in the treatment of a number of conditions including human immunodeficiency virus type 1 infection and a variety of cancers.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Booth V,Slupsky CM,Clark-Lewis I,Sykes BDdoi
10.1016/s0022-2836(03)00094-9keywords:
subject
Has Abstractpub_date
2003-03-21 00:00:00pages
329-34issue
2eissn
0022-2836issn
1089-8638pii
S0022283603000949journal_volume
327pub_type
杂志文章abstract：:K- and H-Ras are the most commonly mutated genes in human tumors and are critical for conferring and maintaining the oncogenic phenotype in tumors with poor prognoses. Here, we design genetically encoded antibody-like ligands (intrabodies) that recognize active, GTP-bound K- and H-Ras. These ligands, which use the 10t...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2016.11.008
更新日期：2017-02-17 00:00:00
abstract：:The hydroxyl radical footprint of the TATA-binding protein (TBP) bound to the high-affinity sequence TATAAAAG of the adenovirus 2 major late promoter has been quantitatively compared to a 2 ns molecular dynamics simulation of the complex in aqueous solution at room temperature using the CHARMM23 potential. The nucleot...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2000.4173
更新日期：2000-11-17 00:00:00
abstract：:Close interactions of the C-H...O type are known to occur in a variety of organic crystals, although it had been often argued that they do not represent true hydrogen bonds. During an extensive comparative study of all structurally characterized serine hydrolases containing an Asp(Glu)-His-Ser catalytic triad at their...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1475
更新日期：1994-08-05 00:00:00
abstract：:Activation of family A G-protein-coupled receptors involves a rearrangement of a conserved interhelical cytoplasmic hydrogen bond network between the E(D)RY motif on transmembrane helix 3 (H3) and residues on H6, which is commonly termed the cytoplasmic "ionic lock." Glu134(3.49) of the E(D)RY motif also forms an intr...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2008.05.022
更新日期：2008-07-18 00:00:00
abstract：:We report the X-ray structure analysis and refinement at 1.9 A resolution of calf gamma-II crystallin, a lens-specific protein. The sequence of Croft (1972) has been modified to give a polypeptide chain of 174 residues (cf. 165). The protein has a symmetrical, hierarchical structure of two globular domains each compri...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(83)80232-0
更新日期：1983-10-15 00:00:00
abstract：:The SfiI endonuclease is a prototype for DNA looping. It binds two copies of its recognition sequence and, if Mg(2+) is present, cuts both concertedly. Looping was examined here on supercoiled and relaxed forms of a 5.5 kb plasmid with three SfiI sites: sites 1 and 2 were separated by 0.4 kb, and sites 2 and 3 by 2.0 ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.03.046
更新日期：2004-05-21 00:00:00
abstract：:Many proteins are composed of independently-folded domains connected by flexible linkers. The primary sequence and length of such linkers can set the effective concentration for the tethered domains, which impacts rates of association and enzyme activity. The length of such linkers can be sensitive to environmental co...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2020.166793
更新日期：2021-01-01 00:00:00
abstract：:Although many putative heme transporters have been discovered, it has been challenging to prove that these proteins are directly involved with heme trafficking in vivo and to identify their heme binding domains. The prokaryotic pathways for cytochrome c biogenesis, Systems I and II, transport heme from inside the cell...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2018.01.022
更新日期：2018-04-13 00:00:00
abstract：:With a view to obtaining a more complete view of the composition and structure of the thick filaments of vertebrate skeletal muscle, we have isolated and characterized two new myofibrillar components, H-protein and X-protein. These were purified by hydroxyapatite column chromatography of an impure C-protein preparatio...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(83)80127-2
更新日期：1983-11-05 00:00:00
abstract：:GTP and Ca2+, two well-known modulators of intracellular signaling pathways, control a structural/functional switch between two vital and mutually exclusive activities, cross-linking and Galpha activity, in the same enzyme. The enzyme, a brain-derived tissue-type transglutaminase (TGase), was recently cloned by us in ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.2052
更新日期：1998-10-02 00:00:00
abstract：:A homologue of the Escherichia coli GroEL apical domain was obtained from thermophilic eubacterium Thermus thermophilus. The domains share 70 % sequence identity (101 out of 145 residues). The thermal stability of the T. thermophilus apical domain (Tm>100 degrees C as evaluated by circular dichroism) is at least 35 de...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2000.4405
更新日期：2001-02-23 00:00:00
abstract：:RanBPM and RanBP10 are non-canonical members of the Ran binding protein family that lack the Ran binding domain and do not associate with Ran GTPase in vivo. Rather, they have been shown to be scaffolding proteins that are important for a variety of cellular processes, and both of these proteins contain a SPRY domain,...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2016.09.004
更新日期：2016-10-23 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：:Ionotropic glutamate receptors (iGluRs) mediate excitatory neurotransmission in the central nervous system and play key roles in brain development and disease. iGluRs have two distinct extracellular domains, but the functional role of the distal N-terminal domain (NTD) is poorly understood. Crystal structures of the N...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2011.09.037
更新日期：2011-11-18 00:00:00
abstract：:Using HU chemical nucleases to probe HU-DNA interactions, we report here for the first time site-specific binding of HU to naked DNA. An unique feature of this interaction is the absolute requirement for negative DNA supercoiling for detectable levels of site-specific DNA binding. The HU binding site is the Mu spacer ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1999.2805
更新日期：1999-06-18 00:00:00
abstract：:The asymmetric unit membrane (AUM) forms numerous plaques covering the apical surface of mammalian urinary bladder epithelium. These plaques contain four major integral membrane proteins called uroplakins Ia, Ib, II and III, which form particles arranged in a well-ordered hexagonal lattice with p6 symmetry and a latti...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1995.0269
更新日期：1995-05-19 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：:Human cytidine deaminase apolipoprotein B mRNA-editing catalytic polypeptide-like 3F (APOBEC3F, or A3F), like APOBEC3G, has broad antiviral activity against diverse retroelements, including Vif-deficient human immunodeficiency virus (HIV)-1. Its antiviral functions are known to rely on its virion encapsidation and be ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2007.11.017
更新日期：2008-01-25 00:00:00
abstract：:Determining the relationship between protein folding pathways on and off the ribosome remains an important area of investigation in biology. Studies on isolated domains have shown that alteration of the separation of residues in a polypeptide chain, while maintaining their spatial contacts, may affect protein stabilit...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2018.10.011
更新日期：2018-12-07 00:00:00
abstract：:Porins, such as Escherichia coli OmpF, provide the only reported example of a voltage-gated channel where the three-dimensional structure is known to high resolution. Mutations that affect voltage-gating are clustered around the eyelet region, which is a mid-channel constriction caused by a polypeptide loop (L3) foldi...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1997.1474
更新日期：1998-01-16 00:00:00
abstract：:Natural products are a valuable source for novel lead structures in drug discovery, but for the majority of isolated bioactive compounds, the cellular targets are unknown. The structurally unique ansa-polyketide kendomycin (KM) was reported to exert its potent cytotoxic effects via impairment of the ubiquitin proteaso...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2014.06.019
更新日期：2014-09-09 00:00:00
abstract：:UDP-glucose is the universal activated form of glucose, employed in all organisms for glucosyl transfer reactions and as precursor for various activated carbohydrates. In animal and fungal metabolism, UDP-glucose is required for utilization of galactose and for the synthesis of glycogen, the major carbohydrate storage...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2006.08.079
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：:Bacteriophage with double-stranded, linear DNA genomes package DNA into pre-assembled icosahedral procapsids through a unique vertex. The packaging vertex contains an oligomeric ring of a portal protein that serves as a recognition site for the packaging enzymes, a conduit for DNA translocation, and the site of tail a...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2001.5275
更新日期：2002-02-01 00:00:00
abstract：:Detachment of flagella in Chlamydomonas reinhardii stimulates a rapid accumulation of tubulin mRNAs. The induced tubulin mRNAs are normally rapidly degraded following flagellar regeneration, but inhibition of protein synthesis with cycloheximide prevents their degradation. alpha-Tubulin poly(A) tail lengths were measu...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(89)90243-x
更新日期：1989-06-20 00:00:00
abstract：:The membrane assembly of the respiratory complexes requires the membrane insertases Oxa1 in mitochondria and YidC in bacteria. Oxa1 is responsible for the insertion of the mitochondrial cytochrome c oxidase subunit II (CoxII). Here, we investigated whether YidC, the bacterial Oxa1 homolog, plays a crucial role in the ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2006.01.030
更新日期：2006-04-14 00:00:00
abstract：:Mutations at solvent-inaccessible core positions in proteins can impact function through many biophysical mechanisms including alterations to thermodynamic stability and protein dynamics. As these properties of proteins are difficult to investigate, the impacts of core mutations on protein function are poorly understo...
journal_title：Journal of molecular biology
pub_type： 评论,杂志文章
doi：10.1016/j.jmb.2013.10.042
更新日期：2014-04-03 00:00:00
abstract：:While the disulfide bridge is highly conserved within the immunoglobulin fold, a few antibody variable domains lack one of the essential cysteine residues. In the levan binding antibody ABPC48 one of the essential cysteine residues (Cys H92) of the heavy chain variable domain is replaced by tyrosine. We expressed scFv...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1996.0726
更新日期：1997-01-17 00:00:00
abstract：:Cobalamin-independent methionine synthase (MetE) catalyzes the direct transfer of a methyl group from methyltetrahydrofolate to l-homocysteine to form methionine. Previous studies have shown that the MetE active site coordinates a zinc atom, which is thought to act as a Lewis acid and plays a role in the activation of...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2011.08.005
更新日期：2011-09-30 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
