Enzymes are proteins that catalyze chemical reactions. A protein is simply a polypeptide
composed of amino acids linked by a peptide bond, and the term generally, but
not always, refers to the folded conformation. To understand how an enzyme functions,
including its binding and functional properties, it is necessary to know the
properties of the amino acids and how the amino acids are linked together, including
the torsion angles of the bonds and the space occupied, and the interactions of the
atoms leading to the final conformations of the folded protein.
The RNA folding trajectory features numerous off-pathway folding traps,
which represent conformations that are often equally as stable as the native
functional ones. Therefore, the conversion between these off-pathway struc-tures and the native correctly folded ones is the critical step in RNA fold-ing.
The active site of triosephosphate isomerase (TIM, EC: 188.8.131.52), a
dimeric enzyme, lies very close to the subunit interface. Attempts to
engineer monomeric enzymes have yielded well-folded proteins with dra-matically reduced activity.
Aconitases are iron–sulfur hydrolyases catalysing the interconversion of cit-rate and isocitrate in a wide variety of organisms. Eukaryotic aconitases
have been assigned additional roles, as in the case of the metazoan dual
activity cytosolic aconitase–iron regulatory protein 1 (IRP1). This human
protein was produced in yeast mitochondria to probe IRP1 folding in this
organelle where iron–sulfur synthesis originates.
This paper presents a dependency language model (DLM) that captures linguistic constraints via a dependency structure, i.e., a set of probabilistic dependencies that express the relations between headwords of each phrase in a sentence by an acyclic, planar, undirected graph. Our contributions are three-fold. First, we incorporate the dependency structure into an n-gram language model to capture long distance word dependency. Second, we present an unsupervised learning method that discovers the dependency structure of a sentence using a bootstrapping procedure. ...
It has been reported that a human chloride intracellular channel (CLIC)
protein, CLIC4, translocates to the nucleus in response to cellular stress,
facilitated by a putative CLIC4 nuclear localization signal (NLS). The
CLIC4 NLS adopts ana-helical structure in the native CLIC4 fold.
A carboxylesterase with ab-lactamase fold from Arthrobacterpossesses a
low level of hydrolytic activity (0.023 lmolÆmin
) when acting on a
6-aminohexanoate linear dimer byproduct of the nylon-6 industry (Ald).
G181D⁄H266N⁄D370Y triple mutations in the parental esterase increased
the Ald-hydrolytic activity 160-fold.
The chi (v)and psi(w) subunits of Escherichia coliDNA
polymerase III formaheterodimer that is associatedwith the
ATP-dependent clamp-loadermachinery. InE. coli,thev:w
heterodimer serves as a bridge between the clamp-loader
complex and the single-strandedDNA-binding protein. We
determined the crystal structure of thev:wheterodimer at
The crystal structures of the wild-type HIV-1 protease (PR)
and the two resistant variants, PRV82Aand PRL90M,have
been determined in complex with the antiviral drug, indi-navir, to gain insight into the molecular basis of drug
resistance. V82A and L90M correspond to an active site
mutation and nonactive site mutation, respectively. The
inhibition (Ki)of PRV82Aand PRL90Mwas 3.3- and 0.16-fold, respectively, relative to the value for PR. They showed
only a modest decrease, of 10–15%, in theirkcat
relative to PR. ...
To facilitate the process of proteindesign and learn the basic
rules that control the structure and stability of proteins,
combinatorial methods have been developed to select or
screen proteins with desired properties from libraries of
mutants. One such method uses phage-display and proteo-lysis to select stably folded proteins. This method does not
rely on specific properties of proteins for selection. There-fore, in principle it can be applied to any protein.
The changes in the far-UV CD signal, intrinsic tryptophan
fluorescence and bilirubin absorbance showed that the
guanidine hydrochloride (GdnHCl)-induced unfolding of
a multidomain protein, human serum albumin (HSA),
followed a two-state process. However, using environment
sensitive Nile red fluorescence, the unfolding and folding
pathways ofHSA were found to followa three-state process
andanintermediatewas detectedinthe range0.25–1.5M
There are several different families of repeat proteins. In each, a distinct
structural motif is repeated in tandem to generate an elongated structure.
The nonglobular, extended structures that result are particularly well suited
to present a large surface area and to function as interaction domains.
Many repeat proteins have been demonstrated experimentally to fold and
function as independent domains.
In this paper, we present a structural learning model for joint sentiment classiﬁcation and aspect analysis of text at various levels of granularity. Our model aims to identify highly informative sentences that are aspect-speciﬁc in online custom reviews.
The solution structure of the growth factor chimera mEGF/ TGFa44250 has been determined using an extended version of the DYANA procedure for calculating structures from NMR data. The backbone fold and preferred orientation of the domains of the chimera are similar to those found in previous studies of EGF structures, and several H-bonds used as input constraints in those studies were found independently in the chimera. This shows that the modiﬁed activity of the chimera does not result from a major structural change.
After studying this chapter you will be able to: Know that primary structure determines protein conformation, define domains, motifs combine through hydrophobic interactions to form domains, know general properties of a protein with 4o structure, know the definition of an oligomeric protein, know 4o structure nomenclature, be able to determine the subunit composition of an oligomeric protein using information obtained from gel permeation chromatography and SDS PAGE analysis,...
To elucidate the architectural principle of protein structure, we focused on
sequestration from solvent, which is a common characteristic of folding
and self-associative precipitation. Because protein solubility can be
regarded as a basis for the potential ability to sequester from solvent, we
assume that poorly soluble proteins tend not only to precipitate, but also
to form solution structures.
Proteins possessing deeply embedded topological knots in their structure
add a stimulating new challenge to the already complex protein-folding
problem. The most complicated knotted topology observed to date belongs
to the human enzyme ubiquitin C-terminal hydrolase UCH-L3, which is an
integral part of the ubiquitin–proteasome system.
Neuroglobin is a recently discovered member of the globin family, mainly
observed in neurons and retina. Despite the low sequence identity (less
than 20% over the whole sequence for the human proteins), the general
fold of neuroglobin closely resembles that of myoglobin. The latter is a
paradigmatic protein for folding studies, whereas much less is known about
the neuroglobin folding pathway.
Pyridoxal 5¢-phosphate-dependent enzymes may be grouped into five struc-tural superfamilies of proteins, corresponding to as many fold types. The
fold type I is by far the largest and most investigated group. An important
feature of this fold, which is characterized by the presence of two domains,
appears to be the existence of three clusters of evolutionarily conserved
Small heat shock proteins (sHsps) are intracellular molecular chaperones
that prevent the aggregation and precipitation of partially folded and
destabilized proteins. sHsps comprise an evolutionarily conserved region of
80–100 amino acids, denoted thea-crystallin domain, which is flanked by
regions of variable sequence and length: the N-terminal domain and the