Core Site-Moiety Maps Reveal Inhibitors and Binding Mechanisms of Orthologous Proteins by Screening Compound Libraries

Members of protein families often share conserved structural subsites for interaction with chemically similar moieties despite low sequence identity. We propose a core site-moiety map of multiple proteins (called CoreSiMMap) to discover inhibitors and mechanisms by profiling subsite-moiety interactions of immense screening compounds. The consensus anchor, the subsite-moiety interactions with statistical significance, of a CoreSiMMap can be regarded as a “hot spot” that represents the conserved binding environments involved in biological functions. Here, we derive the CoreSiMMap with six consensus anchors and identify six inhibitors (IC50<8.0 µM) of shikimate kinases (SKs) of Mycobacterium tuberculosis and Helicobacter pylori from the NCI database (236,962 compounds). Studies of site-directed mutagenesis and analogues reveal that these conserved interacting residues and moieties contribute to pocket-moiety interaction spots and biological functions. These results reveal that our multi-target screening strategy and the CoreSiMMap can increase the accuracy of screening in the identification of novel inhibitors and subsite-moiety environments for elucidating the binding mechanisms of targets

Measurement of Exclusive B Decays to Final States Containing a Charmed Baryon

Using data collected by the CLEO detector in the Upsilon(4S) region, we report new measurements of the exclusive decays of B mesons into final states of the type Lambda_c^+ p-bar n(pi), where n=0,1,2,3. We find signals in modes with one, two and three pions and an upper limit for the two body decay Lambda_c^+ pbar. We also make the first measurements of exclusive decays of B mesons to Sigma_c p-bar n(pi), where n=0,1,2. We find signals in modes with one and two pions and an upper limit for the two body decay Sigma_c p-bar. Measurements of these modes shed light on the mechanisms involved in B decays to baryons.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Measurement of the Masses and Widths of the Sigma_c^++ and Sigma_c^0 Charmed Baryons

Using data recorded by the CLEO II and CLEO II.V detector configurations at CESR, we report new measurements of the masses of the Sigma_c^{++} and Sigma_c^0 charmed baryons, and the first measurements of their intrinsic widths. We find M(Sigma_c^{++}) - M(Lambda_c^+) = 167.4 +- 0.1 +- 0.2 MeV, Gamma(Sigma_c^{++}) = 2.3 +- 0.2 +- 0.3 MeV, and M(Sigma_c^0) - M(Lambda_c^+) = 167.2 +- 0.1 +- 0.2 MeV, Gamma(Sigma_c^0) = 2.5 +- 0.2 +- 0.3 MeV, where the uncertainties are statistical and systematic, respectively.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PRD, Rapid Communications. Reference [13] correcte

Evidence for the Decay D0→K+π−π+π−D^0\to K^+ \pi^-\pi^+\pi^-

We present a search for the ``wrong-sign'' decay D0 -> K+ pi- pi+ pi- using 9 fb-1 of e+e- collisions on and just below the Upsilon(4S) resonance. This decay can occur either through a doubly Cabibbo-suppressed process or through mixing to a D0bar followed by a Cabibbo-favored process. Our result for the time-integrated wrong-sign rate relative to the decay D0 -> K- pi+ pi- pi+ is (0.0041 +0.0012-0.0011(stat.) +-0.0004(syst.))x(1.07 +-0.10)(phase space), which has a statistical significance of 3.9 standard deviations.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Hadronic Mass Moments in Inclusive Semileptonic B Meson Decays

We have measured the first and second moments of the hadronic mass-squared distribution in B -> X_c l nu, for P(lepton) > 1.5 GeV/c. We find <M_X^2 - M_D[Bar]^2> = 0.251 +- 0.066 GeV^2, )^2 > = 0.576 +- 0.170 GeV^4, where M_D[Bar] is the spin-averaged D meson mass. From that first moment and the first moment of the photon energy spectrum in b -> s gamma, we find the HQET parameter lambda_1 (MS[Bar], to order 1/M^3 and beta_0 alpha_s^2) to be -0.24 +- 0.11 GeV^2. Using these first moments and the B semileptonic width, and assuming parton-hadron duality, we obtain |V_cb| = 0.0404 +- 0.0013.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Observation of Exclusive barB --> D(*) K*- Decays

We report the first observation of the exclusive decays \bar B\to D^{(*)}K^{*-}, using 9.66 x 10^{6} B\bar{B} pairs collected at the \Upsilon(4S) with the CLEO detector. We measure the following branching fractions: {\cal B}(B^- -> D^0 K^{*-})=(6.1 +- 1.6 +-1.7)x10^{-4}, {\cal B}(\bar{B^0} -> D^+K^{*-})=(3.7 +- 1.5 +- 1.0) x 10^{-4}, {\cal B}(\bar{B^0} -> D^{*+}K^{*-})=(3.8 +- 1.3 +- 0.8) x 10^{-4} and {\cal B}(B^- --> D^{*0} K^{*-})=(7.7 +- 2.2 +- 2.6) x 10^{-4}. The \bar B ->D^*K^{*-} branching ratios are the averages of those corresponding to the 00 and 11 helicity states. The errors shown are statistical and systematic, respectively.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, Published in Phys.Rev.Lett.88:101803,200

Observation of the Ωc0\Omega_{c}^{0} Charmed Baryon at CLEO

The CLEO experiment at the CESR collider has used 13.7 fb$^{-1}$ of data to search for the production of the $\Omega_c^0$ (css-ground state) in $e^{+}e^{-}$ collisions at $\sqrt{s} \simeq 10.6$ {\rm GeV}. The modes used to study the $\Omega_c^0$ are $\Omega^- \pi^+$, $\Omega^- \pi^+ \pi^0$, $\Xi^- K^- pi^+ \pi^+$, $\Xi^0 K^- pi^+$, and $\Omega^- \pi^+ \pi^- \pi^+$. We observe a signal of 40.4$\pm$9.0(stat) events at a mass of 2694.6$\pm$2.6(stat)$\pm$1.9(syst) {\rm MeV/$c^2$}, for all modes combined.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN