The recent outbreak of pneumonia-causing COVID-19 in China is an urgent global public health issue with an increase in mortality and morbidity. Here we report our modelled homo-trimer structure of COVID-19 spike glycoprotein in both closed (ligand-free) and open (ligand-bound) conformation, which is involved in host cell adhesion. We also predict the unique N-and O-linked glycosylation sites of spike glycoprotein that distinguish it from the SARS and underlines shielding and camouflage of COVID-19 from the host the defence system. Furthermore, our study also highlights the key finding that the S1 domain of COVID-19 spike glycoprotein potentially interacts with the human CD26, a key immunoregulatory factor for hijacking and virulence. These findings accentuate the unique features of COVID-19 and assist in the development of new therapeutics.

The structure of the proline-specific aminopeptidase (EC 3.4.11.9) from Escherichia coli has been solved and refined for crystals of the native enzyme at a 2.0-Å resolution, for a dipeptide-inhibited complex at 2.3-Å resolution, and for a low-pH inactive form at 2.7-Å resolution. The protein crystallizes as a tetramer, more correctly a dimer of dimers, at both high and low pH, consistent with observations from analytical ultracentrifuge studies that show that the protein is a tetramer under physiological conditions. The monomer folds into two domains. The active site, in the larger C-terminal domain, contains a dinuclear manganese center in which a bridging water molecule or hydroxide ion appears poised to act as the nucleophile in the attack on the scissile peptide bond of Xaa-Pro. The metal-binding residues are located in a single subunit, but the residues surrounding the active site are contributed by three subunits. The fold of the protein resembles that of creatine amidinohydrolase (creatinase, not a metalloenzyme). The C-terminal catalytic domain is also similar to the single-domain enzyme methionine aminopeptidase that has a dinuclear cobalt center.Proline-specific peptidases have been described in a wide variety of organisms and specifically cleave either the amide bond after a proline residue or the imide bond that precedes it (1). Proline aminopeptidases (EC 3.4.11.9) specifically release the N-terminal residue from a peptide where the penultimate residue is proline. These enzymes have significant sequence homology with (i) some other amino peptidases (e.g., methionine aminopeptidase, AMPM) and (ii) the Xaa-Pro dipeptidases, prolidases, that specifically cleave Xaa-Pro dipeptides. All these enzymes are activated in the presence of divalent metal ions, though the biologically active metal is not always certain. In vitro the prolyl peptidases are most active in the presence of Mn 2ϩ . Structural comparisons between AMPM and creatine amidinohydrolase (creatinase) and sequence comparisons between these proteins and aminopeptidase P (AMPP) and prolidase have suggested that the catalytic domains of all four enzymes have a common fold (2). This work presents the crystal structure of AMPP, the product of the pepP gene in Escherichia coli. The structures of a complex of AMPP with a dipeptide inhibitor and a low-pH inactive form are used to devise a plausible mechanism for peptide hydrolysis. EXPERIMENTAL PROCEDURESOverexpression and Purification of AMPP. AMPP was originally isolated and characterized in E. coli (3) and was subsequently cloned and overexpressed (4). The details of the overexpression and purification of AMPP used in this work will be published elsewhere. Briefly, AMPP was overexpressed in the E. coli AN1459͞pPL670. Lysed cells were subject to (NH 4 ) 2 SO 4 precipitation at 4°C followed by centrifugation. The pellet was resuspended and applied to a DEAE-Fractogel column (Merck). The AMPP-containing fraction was then passed over a ceramic hydroxyapatite column (Bio-Rad). This simple purifi...

Steroid receptor RNA activator (SRA), the only known RNA coactivator, augments transactivation by nuclear receptors (NRs). We identified SLIRP (SRA stem-loop interacting RNA binding protein) binding to a functional substructure of SRA, STR7. SLIRP is expressed in normal and tumor tissues, contains an RNA recognition motif (RRM), represses NR transactivation in a SRA- and RRM-dependent manner, augments the effect of Tamoxifen, and modulates association of SRC-1 with SRA. SHARP, a RRM-containing corepressor, also binds STR7, augmenting repression with SLIRP. SLIRP colocalizes with SKIP (Chr14q24.3), another NR coregulator, and reduces SKIP-potentiated NR signaling. SLIRP is recruited to endogenous promoters (pS2 and metallothionein), the latter in a SRA-dependent manner, while NCoR promoter recruitment is dependent on SLIRP. The majority of the endogenous SLIRP resides in the mitochondria. Our data demonstrate that SLIRP modulates NR transactivation, suggest it may regulate mitochondrial function, and provide mechanistic insight into interactions between SRA, SLIRP, SRC-1, and NCoR.