278 research outputs found
Accounting for epistatic interactions improves the functional analysis of protein structures
Motivation: The constraints under which sequence, structure and function coevolve are not fully understood. Bringing this mutual relationship to light can reveal the molecular basis of binding, catalysis and allostery, thereby identifying function and rationally guiding protein redesign. Underlying these relationships are the epistatic interactions that occur when the consequences of a mutation to a protein are determined by the genetic background in which it occurs. Based on prior data, we hypothesize that epistatic forces operate most strongly between residues nearby in the structure, resulting in smooth evolutionary importance across the structure. Methods and Results: We find that when residue scores of evolutionary importance are distributed smoothly between nearby residues, functional site prediction accuracy improves. Accordingly, we designed a novel measure of evolutionary importance that focuses on the interaction between pairs of structurally neighboring residues. This measure that we term pair-interaction Evolutionary Trace yields greater functional site overlap and better structure-based proteome-wide functional predictions. Conclusions: Our data show that the structural smoothness of evolutionary importance is a fundamental feature of the coevolution of sequence, structure and function. Mutations operate on individual residues, but selective pressure depends in part on the extent to which a mutation perturbs interactions with neighboring residues. In practice, this principle led us to redefine the importance of a residue in terms of the importance of its epistatic interactions with neighbors, yielding better annotation of functional residues, motivating experimental validation of a novel functional site in LexA and refining protein function prediction. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online
Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation.
The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01â
Ă
using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation
Bounding Anomalous Gauge-Boson Couplings
In this version we have corrected some minor errors in the tables, corrected
typos, and added a reference. We have also updated our comparison with earlier
workers. Figures are now included as uuencoded compressed tar files.Comment: 32 page
Bilocal expansion of the Borel amplitude and the hadronic tau decay width
The singular part of Borel transform of a QCD amplitude near the infrared
renormalon can be expanded in terms of higher order Wilson coefficients of the
operators associated with the renormalon. In this paper we observe that this
expansion gives nontrivial constraints on the Borel amplitude that can be used
to improve the accuracy of the ordinary perturbative expansion of the Borel
amplitude. In particular, we consider the Borel transform of the Adler function
and its expansion around the first infrared renormalon due to the gluon
condensate. Using the next-to-leading order Wilson coefficient of the gluon
condensate operator, we obtain an exact constraint on the Borel amplitude at
the first IR renormalon. We then extrapolate, using judiciously chosen
conformal transformations and Pade approximants, the ordinary perturbative
expansion of the Borel amplitude in such a way that this constraint is
satisfied. This procedure allows us to predict the coefficient
of the Adler function, which gives a result consistent with the estimate by
Kataev and Starshenko using a completely different method. We then apply this
improved Borel amplitude to the tau decay width, and obtain the strong coupling
constant . We then compare this result with those of
other resummation methods.Comment: 30 pages, 4 eps-figures, revtex; version as appears in PRD; no major
changes; more careful rounding of some number
Model-Independent Global Constraints on New Physics
Using effective-lagrangian techniques we perform a systematic survey of the
lowest-dimension effective interactions through which heavy physics might
manifest itself in present experiments. We do not restrict ourselves to special
classes of effective interactions (such as `oblique' corrections). We compute
the effects of these operators on all currently well-measured electroweak
observables, both at low energies and at the resonance, and perform a
global fit to their coefficients. Despite the fact that a great many operators
arise in our survey, we find that most are quite strongly bounded by the
current data. We use our survey to systematically identify those effective
interactions which are {\it not} well-bounded by the data -- these could very
well include large new-physics contributions. Our results may also be used to
efficiently confront specific models for new physics with the data, as we
illustrate with an example.Comment: plain TeX, 68 pages, 2 figures (postscript files appended),
McGill-93/12, NEIPH-93-008, OCIP/C-93-6, UQAM-PHE-93/08, UdeM-LPN-TH-93-15
Structure of a putative NTP pyrophosphohydrolase: YP_001813558.1 from Exiguobacterium sibiricum 255-15.
The crystal structure of a putative NTPase, YP_001813558.1 from Exiguobacterium sibiricum 255-15 (PF09934, DUF2166) was determined to 1.78â
Ă
resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-α-helical NTP pyrophosphatases. In dimeric dUTPase-like proteins, a central four-helix bundle forms the active site. However, in YP_001813558.1, an unexpected intertwined swapping of two of the helices that compose the conserved helix bundle results in a `linked dimer' that has not previously been observed for this family. Interestingly, despite this novel mode of dimerization, the metal-binding site for divalent cations, such as magnesium, that are essential for NTPase activity is still conserved. Furthermore, the active-site residues that are involved in sugar binding of the NTPs are also conserved when compared with other α-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity
Uses and Abuses of Effective Lagrangians
Motivated by past and recent analyses we critically re-examine the use of
effective lagrangians in the literature to constrain new physics and to
determine the `physics reach' of future experiments. We demonstrate that many
calculations, such as those involving anomalous trilinear gauge-boson
couplings, either considerably overestimate loop-induced effects, or give
ambiguous answers. The source of these problems is the use of cutoffs to
evaluate the size of such operators in loop diagrams. In contrast to other
critics of these loop estimates, we prove that the inclusion of
nonlinearly-realized gauge invariance into the low-energy lagrangian is
irrelevant to this conclusion. We use an explicit example using known
multi-Higgs physics above the weak scale to underline these points. We show how
to draw conclusions regarding the nature of the unknown high-energy physics
without making reference to low-energy cutoffs.Comment: 36 page
Structure of the Îł-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-Îł-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases.
Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC from Bacillus subtilis have both previously been characterized as highly specific Îł-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC ortholog from Bacillus cereus (BcYkfC) at 1.8â
Ă
resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain that is ubiquitous in the very large family of cell-wall-related cysteine peptidases. A bound reaction product (L-Ala-Îł-D-Glu) enabled the identification of conserved sequence and structural signatures for recognition of L-Ala and Îł-D-Glu and, therefore, provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both residues interact with the free amine group of the alanine. This structural feature allows the definition of a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-Îł-D-glutamate endopeptidase that contains the two key components (an NlpC/P60 domain attached to an SH3b domain) for assembly of a YkfC-like active site
The structure of BVU2987 from Bacteroides vulgatus reveals a superfamily of bacterial periplasmic proteins with possible inhibitory function.
Proteins that contain the DUF2874 domain constitute a new Pfam family PF11396. Members of this family have predominantly been identified in microbes found in the human gut and oral cavity. The crystal structure of one member of this family, BVU2987 from Bacteroides vulgatus, has been determined, revealing a ÎČ-lactamase inhibitor protein-like structure with a tandem repeat of domains. Sequence analysis and structural comparisons reveal that BVU2987 and other DUF2874 proteins are related to ÎČ-lactamase inhibitor protein, PepSY and SmpA_OmlA proteins and hence are likely to function as inhibitory proteins
Status of Muon Collider Research and Development and Future Plans
The status of the research on muon colliders is discussed and plans are
outlined for future theoretical and experimental studies. Besides continued
work on the parameters of a 3-4 and 0.5 TeV center-of-mass (CoM) energy
collider, many studies are now concentrating on a machine near 0.1 TeV (CoM)
that could be a factory for the s-channel production of Higgs particles. We
discuss the research on the various components in such muon colliders, starting
from the proton accelerator needed to generate pions from a heavy-Z target and
proceeding through the phase rotation and decay ()
channel, muon cooling, acceleration, storage in a collider ring and the
collider detector. We also present theoretical and experimental R & D plans for
the next several years that should lead to a better understanding of the design
and feasibility issues for all of the components. This report is an update of
the progress on the R & D since the Feasibility Study of Muon Colliders
presented at the Snowmass'96 Workshop [R. B. Palmer, A. Sessler and A.
Tollestrup, Proceedings of the 1996 DPF/DPB Summer Study on High-Energy Physics
(Stanford Linear Accelerator Center, Menlo Park, CA, 1997)].Comment: 95 pages, 75 figures. Submitted to Physical Review Special Topics,
Accelerators and Beam
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