2,745 research outputs found
The MEROPS Database
Many proteins undergo important post-translational proteolytic processing to remove targeting signals and activation peptides, and most proteins undergo proteolytic inactivation and catabolism. The enzymes that hydrolyse the peptide bonds in proteins and peptides are known as peptidases, proteases or proteolytic enzymes. The MEROPS database ("http://merops.sanger.ac.uk":http://merops.sanger.ac.uk) presents the classification and nomenclature of peptidases, their inhibitors and substrates. In 1993 we proposed the scheme for the classification of peptidases that has been internationally accepted, and in 1996 we established the MEROPS database. Protein inhibitors have been included in the database since 2004. About 2% of the genes in a genome encode peptidase homologues, and a further 1% encode protein inhibitors. For example, the human genome has 1037 genes encoding peptidase homologues (of which 643 are known or predicted to be active peptidases) and 433 protein inhibitor genes (of which 144 have been biochemically characterized as inhibitors). 

The MEROPS classification is hierarchical. Sequences are grouped into a peptidase species (each of which is given a unique identifier, for example C01.060 for cathepsin B); peptidase species are grouped into a family (for example C1); and families grouped into a clan (for example CA). To be included in the same protein species, sequences must be derived from the same node on a dendrogram derived from the family sequence alignment and known (or predicted) to share similar specificity. To be included in the same family sequences must be homologous over the sequence domain that contains the active site residues (peptidases) or reactive site (inhibitors). To be included in the same clan, the proteins must share similar tertiary structures (or the same linear arrangement of active site residues if the structure is unknown). Over 117,000 peptidase homologues are classified into 3114 protein species, 205 families and 52 clans, and 12,104 protein inhibitors are classified into 663 protein species, 64 families and 33 clans.

The database includes manually curated summaries for each clan, family and protein species. There are also sequence alignments and manually curated bibliographies (with over 41,000 references) at every level. In addition to protein inhibitors we also include 158 manually curated summaries for synthetic and naturally occurring small molecule inhibitors. There is also a summary page for each organism listing all known homologues and an analysis highlighting significant presences, absences or gene family expansions for organisms with a completely sequenced genome. 

The MEROPS database includes known peptidase substrates: naturally occurring peptides and proteins, and synthetic substrates. Currently there are 4091 cleavages of synthetic substrates and 95,413 cleavages of proteins (of which 74,740 are physiological). Cleavages in proteins are mapped to UniProt entries. An alignment of very close homologues of each substrate sequence is shown, highlighting residues around each cleavage site indicating whether the peptidase is known to accept the amino acid at that position or not. Cleavage sites that are conserved are likely to be physiological; cleavage sites that are not conserved may be pathological for the species in which they occur or coincidental.

The MEROPS data is freely available to download from our FTP site ("http://ftp.sanger.ac.uk/pub/MEROPS":http://ftp.sanger.ac.uk/pub/MEROPS) and via our Distributed Annotation System (DAS) server ("http://das.sanger.ac.uk/das/merops":http://das.sanger.ac.uk/das/merops).

Time and M-theory
We review our recent proposal for a background independent formulation of a
holographic theory of quantum gravity. The present review incorporates the
necessary background material on geometry of canonical quantum theory,
holography and spacetime thermodynamics, Matrix theory, as well as our specific
proposal for a dynamical theory of geometric quantum mechanics, as applied to
Matrix theory. At the heart of this review is a new analysis of the conceptual
problem of time and the closely related and phenomenologically relevant problem
of vacuum energy in quantum gravity. We also present a discussion of some
observational implications of this new viewpoint on the problem of vacuum
energy.Comment: 86 pages, 5 figures, LaTeX, typos fixed, references added, and Sec.
6.2 revised; invited review for Int. J. Mod. Phys.
Molecular gas freeze-out in the pre-stellar core L1689B
C17O (J=2-1) observations have been carried out towards the pre-stellar core
L1689B. By comparing the relative strengths of the hyperfine components of this
line, the emission is shown to be optically thin. This allows accurate CO
column densities to be determined and, for reference, this calculation is
described in detail. The hydrogen column densities that these measurements
imply are substantially smaller than those calculated from SCUBA dust emission
data. Furthermore, the C17O column densities are approximately constant across
L1689B whereas the SCUBA column densities are peaked towards the centre. The
most likely explanation is that CO is depleted from the central regions of
L1689B. Simple models of pre-stellar cores with an inner depleted region are
compared with the results. This enables the magnitude of the CO depletion to be
quantified and also allows the spatial extent of the freeze-out to be firmly
established. We estimate that within about 5000 AU of the centre of L1689B,
over 90% of the CO has frozen onto grains. This level of depletion can only be
achieved after a duration that is at least comparable to the free-fall
timescale.Comment: MNRAS letters. 5 pages, 5 figure
Desorption From Interstellar Ices
The desorption of molecular species from ice mantles back into the gas phase
in molecular clouds results from a variety of very poorly understood processes.
We have investigated three mechanisms; desorption resulting from H_2 formation
on grains, direct cosmic ray heating and cosmic ray induced photodesorption.
Whilst qualitative differences exist between these processes (essentially
deriving from the assumptions concerning the species-selectivity of the
desorption and the assumed threshold adsorption energies, E_t) all three
processes are found to be potentially very significant in dark cloud
conditions. It is therefore important that all three mechanisms should be
considered in studies of molecular clouds in which freeze-out and desorption
are believed to be important.
Employing a chemical model of a typical static molecular core and using
likely estimates for the quantum yields of the three processes we find that
desorption by H_2 formation probably dominates over the other two mechanisms.
However, the physics of the desorption processes and the nature of the dust
grains and ice mantles are very poorly constrained. We therefore conclude that
the best approach is to set empirical constraints on the desorption, based on
observed molecular depletions - rather than try to establish the desorption
efficiencies from purely theoretical considerations. Applying this method to
one such object (L1689B) yields upper limits to the desorption efficiencies
that are consistent with our understanding of these mechanisms.Comment: 11 pages, 5 figures, accepted by MNRAS subject to minor revision
which has been carried ou
Molecules, ices and astronomy
Molecules in interstellar gas and in interstellar ices play a fundamental role in astronomy. However, the formation of the simplest molecule, molecular hydrogen, is still not fully understood. Similarly, although interstellar ice analogues have received much attention in the laboratory, the evolution of ices in the interstellar medium still requires further study. At UCL we have developed two separate experiments to address these issues and explore the following questions: How is H formed on dust-grain surfaces? What is the budget between internal, kinetic and surface energies in the formation process? What are the astronomical consequences of these results? For ices, we ask: How do molecules desorb from pure and from mixed ices in regions warmed by newly formed stars? What can molecules released from ices tell us about the star-formation process? We put our results in the context of other laboratory work and we describe their application to current problems in astronomy
The sub-millimeter properties of broad absorption line quasars
We have carried out the first systematic survey of the sub-millimeter
properties of broad absorption line (BAL) quasars. 30 BAL quasars drawn from a
homogeneously selected sample from the Sloan Digital Sky Survey at redshifts
2<z<2.6 were observed with the SCUBA array at the JCMT to a typical rms
sensitivity of 2.5 mJy. Eight quasars were detected at > 2 sigma significance,
four of which are at > 3 sigma significance. The far-infrared luminosities of
these quasars are > 10^{13} L_solar. There is no correlation of sub-millimeter
flux with either the strength of the broad absorption feature or with absolute
magnitude in our sample. We compare the sub-millimeter flux distribution of the
BAL quasar sample with that of a sample of quasars which do not show BAL
features in their optical spectra and find that the two are indistinguishable.
BAL quasars do not have higher sub-millimeter luminosities than non-BAL
quasars. These findings are consistent with the hypothesis that all quasars
would contain a BAL if viewed along a certain line-of-sight. The data are
inconsistent with a model in which the BAL phenomenon indicates a special
evolutionary stage which co-incides with a large dust mass in the host galaxy
and a high sub-millimeter luminosity. Our work provides constraints on
alternative evolutionary explanations of BAL quasars.Comment: 8 pages, 2 figures, ApJ, in pres
Rotation of the pre-stellar core L1689B
The search for the onset of star formation in pre-stellar cores has focussed
on the identification of an infall signature in the molecular line profiles of
tracer species. The classic infall signature is a double peaked line profile
with an asymmetry in the strength of the peaks such that the blue peak is
stronger. L1689B is a pre-stellar core and infall candidate but new JCMT HCO+
line profile data, presented here, confirms that both blue and red asymmetric
line profiles are present in this source. Moreover, a dividing line can be
drawn between the locations where each type of profile is found. It is argued
that it is unlikely that the line profiles can be interpreted with simple
models of infall or outflow and that rotation of the inner regions is the most
likely explanation. A rotational model is developed in detail with a new 3D
molecular line transport code and it is found that the best type of model is
one in which the rotational velocity profile is in between solid body and
Keplerian. It is firstly shown that red and blue asymmetric line profiles can
be generated with a rotation model entirely in the absence of any infall
motion. The model is then quantitively compared with the JCMT data and an
iteration over a range of parameters is performed to minmize the difference
between the data and model. The results indicate that rotation can dominate the
line profile shape even before the onset of infall.Comment: Accepted by MNRAS, 7 pages, 4 figure
A submillimetre survey of the star-formation history of radio galaxies
We present the results of the first major systematic submillimetre survey of
radio galaxies spanning the redshift range 1 < z < 5. The primary aim of this
work is to elucidate the star-formation history of this sub-class of elliptical
galaxies by tracing the cosmological evolution of dust mass. Using SCUBA on the
JCMT we have obtained 850-micron photometry of 47 radio galaxies to a
consistent rms depth of 1 mJy, and have detected dust emission in 14 cases. The
radio galaxy targets have been selected from a series of low-frequency radio
surveys of increasing depth (3CRR, 6CE, etc), in order to allow us to separate
the effects of increasing redshift and increasing radio power on submillimetre
luminosity. Although the dynamic range of our study is inevitably small, we
find clear evidence that the typical submillimetre luminosity (and hence dust
mass) of a powerful radio galaxy is a strongly increasing function of redshift;
the detection rate rises from 15 per cent at z 2.5,
and the average submillimetre luminosity rises as (1+z)^3 out to z~4. Moreover
our extensive sample allows us to argue that this behaviour is not driven by
underlying correlations with other radio galaxy properties such as radio power,
radio spectral index, or radio source size/age. Although radio selection may
introduce other more subtle biases, the redshift distribution of our detected
objects is in fact consistent with the most recent estimates of the redshift
distribution of comparably bright submillimetre sources discovered in blank
field surveys. The evolution of submillimetre luminosity found here for radio
galaxies may thus be representative of massive ellipticals in general.Comment: 31 pages - 10 figures in main text, 3 pages of figures in appendix.
This revised version has been re-structured, but the analysis and conclusions
have not changed. Accepted for publication in MNRA
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