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X Qiu

Publications and source records attributed to X Qiu.

125 records · Page 7Linked to original sources
PubMed1992

Structure of the hirulog 3-thrombin complex and nature of the S' subsites of substrates and inhibitors.

The X-ray crystallographic structure of the human alpha-thrombin complex with hirulog 3 (a potent, noncleavable hirudin-based peptide of the "hirulog" class containing a beta-homoarginine at the scissile bond), which is isomorphous with that of the hirugen-thrombin crystal structure, was solved at 2.3-A resolution by starting with a model for thrombin derived from the hirugen-thrombin complex and was refined by restrained least squares methods (R = 0.132). Residues of hirulog 3 were well-defined in the electron density, which included most of the pentaglycine linker and the C-terminal helical turn that was disordered in a related structure of thrombin with hirulog 1. The interactions of D-Phe1'-Pro2'-beta-homoArg3' with the active site of thrombin were essentially identical to those of related structures of PPACK- (D-Phe-Pro-Arg chloromethyl ketone) and hirulog 1-thrombin, with the guanidinium function of the arginyl P1 residue forming a hydrogen-bonding ion pair with Asp189 of the S1 site. A noticeable shift in the CA atom of beta-homoArg3' due to the methylene insertion displaces the scissile bond from attack by Ser195, thus imparting proteolytic stability to the beta-homoArg hirulog derivative. Resolution of the pentaglycine spacer, linking N- and C-terminal functional domains into a single oligopeptide bivalent inhibitor, permitted delineation of corresponding S' subsites of thrombin. The position of Gly4' (P1') is stabilized by three hydrogen bonds with His57, Lys60F, and Ser195, while the conformational angles maintained in a strained, nonallowed configuration for non-glycyl amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

[Isolation and mapping of arbitrary single copy DNA fragment located on human chromosome 11p11-q11].

A library of genomic DNA has been constructed in EMBL3 lambda phage, from a Chinese hamster/human lymphocytes somatic cell hybrid carrying human chromosome 11 and 20. Recombinants containing human genomic DNA origin can be isolated from the hybrid cell genomic library by using species-specific probe. 8 single copy fragments have been isolated from 13 recombinants. One of them designated as FD11-1 has been identified on chromosome 11 by hybridized it with hybrid cell clone panel and mapped on chromosome 11p11-q11 by chromosome in situ hybridization. On chromosome 11, 3 linkage groups were reported, which located on 11p15, 11p13 and 11q13 respectively. Therefore, the FD11-1 will supply a new locus on chromosome 11 for linkage analysis. Endonuclease recognizing sites and potential recognizing sites on FD11-1 will guide the further RFLP studies.

Chromosome Mapping↗
PubMedDate not supplied

Polymorphisms in the TAP2 gene and their association with rheumatoid arthritis.

The human major histocompatibility complex (MHC) contains two closely related genes (TAP) that encode a family of transporter proteins. It is known that the TAP genes, like other MHC (class I and class II) genes, are polymorphic. In this study we investigated the polymorphisms in the ATP-binding domain of the TAP2 gene and examined the relationship of these polymorphisms to susceptibility to rheumatoid arthritis (RA). On the basis of the distribution of polymorphisms in these genes, three TAP2 alleles could be identified in homozygous typing cell lines, RA patients and normal subjects: TAP2*0101-1693.G, TAP2*0101-1693.A and TAP2*0201-1693.G. The prevalence of the variant (nucleotide A at position 1693), and thus also of the TAP2*0101-1693.A allele, was significantly (p < 0.006, RR = 4.25) higher in RA patients (35.3%) than in normal controls (11.4%). In addition, the TAP2*0101-1693.A allele showed significant (r = 0.45, p < 0.0003) association with HLA-DR4 only in RA patients and the prevalence of both TAP2*0101-1693.A and DR4 genes gave the highest relative risk (RR = 19.21, p < 0.0002) for RA. These data suggest that the MHC region containing both class II and TAP genes confers the strongest susceptibility to RA, with the highest RR value reported so far. It is likely that the genetic variability in the putative peptide transporter could also be implicated in immunological disorders associated with MHC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Y box-binding trans-regulatory nuclear proteins and susceptibility to rheumatoid arthritis.

OBJECTIVE: Inappropriately high levels of expression of HLA-DR molecules or their expression on inappropriate cells, e.g. synovial tissue and T cells, may result in an aberrant tissue-destructive immune response and thus cause susceptibility to rheumatoid arthritis (RA). METHODS: Patients and controls were typed for HLA-DR antigens by oligonucleotide typing of PCR-amplified DNA. Trans-regulatory nuclear proteins that bind to the Y box in DRB promotors were examined by the gel-mobility shift assay. RESULTS: We found that the trans-regulatory nuclear protein (NF-Y), which binds to the Y box in DRB promoters and which plays a dominant role on the level of the expression and inducibility of DR genes, was absent in 50% of RA patients but not in healthy individuals (0%). Furthermore, we observed that all patients (100%) either lacked the NF-Y protein and/or carried the disease susceptibility DRB1 gene, which gives the highest relative risk value (RR = 46.6; p < 1.6 x 10(-6)) reported so far for susceptibility to RA. CONCLUSION: The absence of the trans-regulatory nuclear protein that binds to the Y box with an inverted CCAAT motif in DRB promotors and the presence of the DRB1 gene with the amino acid motif QKRAA and QRRAA cause susceptibility to RA.

Adult↗