Search

Xylan is a polysaccharide found in plant cell walls. It is considered to be a biodegradable polymer, which does not affect negatively the environment. Sulfated xylan derivatives exhibit valuable bioactive properties, in particular, anticoagulant and hypolipidemic. We report on the development of a new method for sulfation of birch wood xylan. Activators of the sulfation reaction with sulfamic acid have been evaluated. Numerical methods have been used to establish the optimum process parameters that ensure the maximum sulfur content in the reaction product. The incorporation of a sulfate group has been confirmed by infrared and nuclear magnetic resonance spectroscopy, and elemental analysis. The initial and sulfated xylans have been comprehensively studied by theoretical methods and the most favorable conformations of the initial xylan and its sulfate have been established. [ABSTRACT FROM AUTHOR]

Research has been conducted on HIV-1 coreceptor CCR5. The role of sulfated tyrosines in this receptor has been investigated, and the results demonstrate that the primary receptor CD4-induced HIV-1 nutralizing antibodies emulate CCR5, and that tyrosine sulfation contributes to the potency of the human humoral response.

Production of amyloid-[Beta] protein (A[Beta]) is initiated by a [Beta]-secretase that cleaves the A [Beta] precursor protein (APP) at the N terminus of A[Beta] (the [Beta] site). A recently identified aspartyl protease, BACE, cleaves the [Beta] site and at residue 11 within the A[Beta] region of APP. Here we show that BACE2, a BACE homolog, cleaves at the [Beta] site and more efficiently at a different site within A[Beta]. The Flemish missense mutation of APP, implicated in a form of familial Alzheimer's disease, is adjacent to this latter site and markedly increases A[Beta] production by BACE2 but not by BACE. BACE and BACE2 respond identically to conservative [Beta]-site mutations, and alteration of a common active site Arg inhibits [Beta]-site cleavage but not cleavage within A[Beta] by both enzymes. These data suggest that BACE2 contributes to A[Beta] production in individuals bearing the Flemish mutation, and that selective inhibition of these highly similar proteases may be feasible and therapeutically advantageous.

Human angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS coronavirus (SARS-CoV). Here we identify the SARS-CoV spike (S)-protein-binding site on ACE2. We also compare S proteins of SARS-CoV isolated during the 2002–2003 SARS outbreak and during the much less severe 2003–2004 outbreak, and from palm civets, a possible source of SARS-CoV found in humans. All three S proteins bound to and utilized palm-civet ACE2 efficiently, but the latter two S proteins utilized human ACE2 markedly less efficiently than did the S protein obtained during the earlier human outbreak. The lower affinity of these S proteins could be complemented by altering specific residues within the S-protein-binding site of human ACE2 to those of civet ACE2, or by altering S-protein residues 479 and 487 to residues conserved during the 2002–2003 outbreak. Collectively, these data describe molecular interactions important to the adaptation of SARS-CoV to human cells, and provide insight into the severity of the 2002–2003 SARS epidemic. [ABSTRACT FROM AUTHOR]

Plasmodium vivaxis one of fourPlasmodiumspecies that cause human malaria.P. vivaxand a related simian malaria parasite,Plasmodium knowlesi, invade erythrocytes by binding the Duffy antigen/receptor for chemokines (DARC) through their respective Duffy binding proteins. Here we show that tyrosines 30 and 41 of DARC are modified by addition of sulphate groups, and that the sulphated tyrosine 41 is essential for association of the Duffy binding proteins ofP. vivax(PvDBP) andP. knowlesi(PkDaBP) with DARC-expressing cells. These sulphated tyrosines also participate in the association of DARC with each of its four known chemokine ligands. Alteration of tyrosine 41 to phenylalanine interferes with MCP-1, RANTES and MGSA association with DARC, but not with that of IL8. In contrast, alteration of tyrosine 30 to phenylalanine interferes with the association of IL8 with DARC. A soluble sulphated amino-terminal domain of DARC, but not one modified to phenylalanine at residue 41, can be used to block the association of PvDBP and PkDaBP with red blood cells, with an IC50 of approximately 5 nM. These data are consistent with a role for tyrosine sulphation in the association of many or most chemokines with their receptors, and identify a key molecular determinant of erythrocyte invasion byP. vivax. [ABSTRACT FROM AUTHOR]

The analysis of cases of damages of headers of steam generators PGV-1000 is submitted and the recommendations allowing appreciably to lower or avoid of such damages are given. [ABSTRACT FROM AUTHOR]

Viruses require specific cellular receptors to infect their target cells. Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for two divergent coronaviruses, SARS coronavirus (SARS-CoV) and human coronavirus NL63 (HCoV-NL63). In addition to host-cell receptors, lysosomal cysteine proteases are required for productive infection by some viruses. Here we show that SARS-CoV, but not HCoV-NL63, utilizes the enzymatic activity of the cysteine protease cathepsin L to infect ACE2-expressing cells. Inhibitors of cathepsin L blocked infection by SARS-CoV and by a retrovirus pseudotyped with the SARS-CoV spike (S) protein but not infection by HCoV-NL63 or a retrovirus pseudotyped with the HCoV-NL63 S protein. Expression of exogenous cathepsin L substantially enhanced infection mediated by the SARS-CoV S protein and by filovirus GP proteins but not by the HCoV-NL63 S protein or the vesicular stomatitis virus G protein. Finally, an inhibitor of endosomal acidification had substantially less effect on infection mediated by the HCoV-NL63 S protein than on that mediated by the SARS-CoV S protein. Our data indicate that two coronaviruses that utilize a common receptor nonetheless enter cells through distinct mechanisms. [ABSTRACT FROM AUTHOR]

Replication of viruses in species other than their natural hosts is frequently limited by entry and postentry barriers. The coronavirus that causes severe acute respiratory syndrome (SARS-CoV) utilizes the receptor angiotensin-converting enzyme 2 (ACE2) to infect cells. Here we compare human, mouse, and rat ACE2 molecules for their ability to serve as receptors for SARS-CoV. We found that, compared to human ACE2, murine ACE2 less efficiently bound the S1 domain of SARS-CoV and supported less-efficient S protein-mediated infection. Rat ACE2 was even less efficient, at near background levels for both activities. Murine 3T3 cells expressing human ACE2 supported SARS-CoV replication, whereas replication was less than 10% as efficient in the same cells expressing murine ACE2. These data imply that a mouse transgenically expressing human ACE2 may be a useful animal model of SARS. [ABSTRACT FROM AUTHOR]

The chemokine receptor CXCR4 plays critical roles in development, immune function, and human immunodeficiency virus type 1 (HIV-1) entry. Here we demonstrate that, like the CC-chemokine receptors CCR5 and CCR2b, CXCR4 is posttranslationally modified by sulfation of its amino-terminal tyrosines. The sulfate group at tyrosine 21 contributes substantially to the ability of CXCR4 to bind its ligand, stromal derived factor 1 alpha. Tyrosine sulfation plays a less significant role in CXCR4-dependent HIV-1 entry than in CCR5-dependent HIV-1 entry. In some cell lines, CXCR4 is efficiently modified by a chondroitin sulfate chain at serine 18, but neither HIV-1 entry nor stromal derived factor 1 alpha binding was affected by loss of this glycosaminoglycan. These data demonstrate a functional role for tyrosine sulfate in the CXC-chemokine receptor family and underscore a general difference in HIV-1 utilization of CCR5 and CXCR4.