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Qun Liu

Publications and source records attributed to Qun Liu.

At least 55 records · Page 3Linked to original sources

Crystal structure of human CD38 extracellular domain.

Human CD38 is a multifunctional protein involved in diverse functions. As an enzyme, it is responsible for the synthesis of two Ca2+ messengers, cADPR and NAADP; as an antigen, it is involved in regulating cell adhesion, differentiation, and proliferation. Besides, CD38 is a marker of progression of HIV-1 infection and a negative prognostic marker of B-CLL. We have determined the crystal structure of the soluble extracellular domain of human CD38 to 1.9 A resolution. The enzyme's overall topology is similar to the related proteins CD157 and the Aplysia ADP-ribosyl cyclase, except with large structural changes at the two termini. The extended positively charged N terminus has lateral associations with the other CD38 molecule in the crystallographic asymmetric unit. The analysis of the CD38 substrate binding models revealed two key residues that may be critical in controlling CD38's multifunctionality of NAD hydrolysis, ADP-ribosyl cyclase, and cADPR hydrolysis activities.

ADP-ribosyl Cyclase↗

Transient decrease in F-actin may be necessary for translocation of proteins into dendritic spines.

It remains poorly understood as to how newly synthesized proteins that are required to act at specific synapses are translocated into only selected subsets of potentiated dendritic spines. Here, we report that F-actin, a major component of the skeletal structure of dendritic spines, may contribute to the regulation of synaptic specificity of protein translocation. We found that the stabilization of F-actin blocked the translocation of GFP-CaMKII and inhibited the diffusion of 3-kDa dextran into spines (in 2-3 weeks cultures). Neuronal activation in hippocampal slices and cultured neurons led to an increase in the activation (decrease in the phosphorylation) of the actin depolymerization factor, cofilin, and a decrease in F-actin. Furthermore, the induction of long-term potentiation by tetanic stimulation induced local transient depolymerization of F-actin both in vivo and in hippocampal slices (8-10 weeks), and this local F-actin depolymerization was blocked by APV, a N-methyl-D-aspartate (NMDA) receptor antagonist. These results suggest that F-actin may play a role in synaptic specificity by allowing protein translocation into only potentiated spines, gated through its depolymerization, which is probably triggered by the activation of NMDA receptors.

2-Amino-5-phosphonovalerate↗

[Repair of finger deep burn with the island skin flap nourished by the cutaneous nerve nutrient vessel of the dorsum of hand].

OBJECTIVE: To investigate the reverse island skin flap nourished by the cutaneous nerve nutrient vessel of the dorsum of hand in the repair of the finger deep burn. METHODS: Fifteen reverse island skin flaps nourished by the cutaneous nerve nutrient vessel of the dorsum of hand were used to repair finger deep burn in 15 patients. The size of the reverse island skin flap ranged from 5 cm x 3 cm to 3 x 2 cm. RESULTS: All the flaps survived. Postoperative follow-up showed satisfactory results in appearance, function and aesthesia. CONCLUSIONS: The reverse island skin flap nourished by the cutaneous nerve nutrient vessel of the dorsum of hand has reliable blood supply, without damage of a known vessel, can meet the demands of fingertip reconstruction. The flap also has the advantages of minor injury of the donor site, easy manipulation and popularization.

Adult↗

Crystal structure of the cysteine-rich secretory protein stecrisp reveals that the cysteine-rich domain has a K+ channel inhibitor-like fold.

Stecrisp from Trimeresurus stejnegeri snake venom belongs to a family of cysteine-rich secretory proteins (CRISP) that have various functions related to sperm-egg fusion, innate host defense, and the blockage of ion channels. Here we present the crystal structure of stecrisp refined to 1.6-angstrom resolution. It shows that stecrisp contains three regions, namely a PR-1 (pathogenesis-related proteins of group1) domain, a hinge, and a cysteine-rich domain (CRD). A conformation of solvent-exposed and -conserved residues (His60, Glu75, Glu96, and His115) in the PR-1 domain similar to that of their counterparts in homologous structures suggests they may share some molecular mechanism. Three flexible loops of hypervariable sequence surrounding the possible substrate binding site in the PR-1 domain show an evident difference in homologous structures, implying that a great diversity of species- and substrate-specific interactions may be involved in recognition and catalysis. The hinge is fixed by two crossed disulfide bonds formed by four of ten characteristic cysteines in the carboxyl-terminal region and is important for stabilizing the N-terminal PR-1 domain. Spatially separated from the PR-1 domain, CRD possesses a similar fold with two K+ channel inhibitors (Bgk and Shk). Several candidates for the possible functional sites of ion channel blocking are located in a solvent-exposed loop in the CRD. The structure of stecrisp will provide a prototypic architecture for a structural and functional exploration of the diverse members of the CRISP family.

Amino Acid Sequence↗

Purification, characterization, crystallization and preliminary X-ray crystallographic analysis of two novel C-type lectin-like proteins: Aall-A and Aall-B from Deinagkistrodon acutus venom.

Aall-A and Aall-B, two novel heterodimeric snake-venom C-type lectin-like proteins (sv-CLPs), were purified from the venom of Deinagkistrodon acutus from Anhui, China. Strikingly, both these proteins can localize on and congregate human erythrocytes, instead of aiming at the common targets of sv-CLPs such as platelet glycoproteins, von Willebrand factors, coagulant factors etc. The crystals of Aall-A belong to space group P2, with unit-cell parameters a = 105.2, b = 56.2, c = 108.7 A, beta = 100.5 degrees , and diffract to 2.0 A resolution, while the crystals of Aall-B belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 36.8, b = 56.5, c = 149.2 A, and diffract to 2.2 A resolution. To our knowledge, this is the first report of sv-CLPs with this unique function and of their preliminary crystallographic analysis.

Amino Acid Sequence↗

Construction of DNA vaccines and their induced protective immunity against experimental Eimeria tenella infection.

In an attempt to construct a DNA vaccine against chicken coccidiosis, the TA4 gene of Eimeria tenella strain BJ was ligated to the mammalian expression vector pcDNA3.1/Zeo(+) to give pcDNA3.1-TA4 (pcDT). Then, Et1A (E. tenella refractile body gene) was ligated to it, upstream, aiming to be expressed in fusion with TA4, giving pcDNA3.1-Et1A-TA4 (pcDET). The constructed DNA vaccines were given to broilers intramuscularly 10-15 min after the breasts had been pre-treated with 25% sucrose solution. At 7 days after the second vaccination, chickens were challenged with 3 x 10(4) sporulated oocysts of E. tenella BJ. The chickens were killed and the lesion scores of the ceca, the relative body-weight gains and the numbers of oocysts in the ceca of each group of chickens were calculated at day 8 post-inoculation. Results indicated that both pcDT and pcDET could induce protective immunity against coccidial challenge. Their use could obviously reduce oocyst output and alleviate chicken body-weight decrease due to coccidial infection. An anti-coccidial index of 160 was achieved with a treatment of 50 microg pcDET and 100 microg pcDT.

Animals↗

The atomic resolution crystal structure of atratoxin determined by single wavelength anomalous diffraction phasing.

By using single wavelength anomalous diffraction phasing based on the anomalous signal from copper atoms, the crystal structure of atratoxin was determined at the resolution of 1.5 A and was refined to an ultrahigh resolution of 0.87 A. The ultrahigh resolution electron density maps allowed the modeling of 38 amino acid residues in alternate conformations and the location of 322 of 870 possible hydrogen atoms. To get accurate information at the atomic level, atratoxin-b (an analog of atratoxin with reduced toxicity) was also refined to an atomic resolution of 0.92 A. By the sequence and structural comparison of these two atratoxins, Arg(33) and Arg(36) were identified to be critical to their varied toxicity. The effect of copper ions on the distribution of hydrogen atoms in atratoxin was discussed, and the interactions between copper ions and protein residues were analyzed based on a statistical method, revealing a novel pentahedral copper-binding motif.

Amino Acid Motifs↗

Crystal structure of a heat-resilient phytase from Aspergillus fumigatus, carrying a phosphorylated histidine.

In order to understand the structural basis for the high thermostability of phytase from Aspergillus fumigatus, its crystal structure was determined at 1.5 A resolution. The overall fold resembles the structure of other phytase enzymes. Aspergillus niger phytase shares 66% sequence identity, however, it is much less heat-resistant. A superimposition of these two structures reveals some significant differences. In particular, substitutions with polar residues appear to remove repulsive ion pair interactions and instead form hydrogen bond interactions, which stabilize the enzyme; the formation of a C-terminal helical capping, induced by arginine residue substitutions also appears to be critical for the enzyme's ability to refold to its active form after denaturation at high temperature. The heat-resilient property of A.fumigatus phytase could be due to the improved stability of regions that are critical for the refolding of the protein; and a heat-resistant A.niger phytase may be achieved by mutating certain critical residues with the equivalent residues in A.fumigatus phytase. Six predicted N-glycosylation sites were observed to be glycosylated from the experimental electron density. Furthermore, the enzyme's catalytic residue His59 was found to be partly phosphorylated and thus showed a reaction intermediate, providing structural insight, which may help understand the catalytic mechanism of the acid phosphatase family. The trap of this catalytic intermediate confirms the two-step catalytic mechanism of the acid histidine phosphatase family.

6-Phytase↗

Purification, partial characterization, crystallization and preliminary X-ray diffraction of two cysteine-rich secretory proteins from Naja atra and Trimeresurus stejnegeri venoms.

Cysteine-rich secretory proteins (CRISPs) are widely distributed in mammals and snake venoms. They possess apparent homology but varying functions. The structure of CRISPs has remained elusive. Two novel members of the family, natrin and stecrisp, have been purified from Naja atra and Trimeresurus stejnegeri venoms, respectively. Their crystals diffract X-rays to resolution limits of 2.1 and 1.6 angstroms, respectively, and belong to the orthorhombic system with different space groups, unit-cell parameters and numbers of molecules per asymmetric unit. Their structures will contribute a structural basis for further functional studies of this family.

Amino Acid Sequence↗

Purification, partial characterization, crystallization and structural determination of AHP-LAAO, a novel L-amino-acid oxidase with cell apoptosis-inducing activity from Agkistrodon halys pallas venom.

A snake-venom protein named AHP-LAAO has been purified from Agkistrodon halys pallas venom using four-stage chromatography. AHP-LAAO is a novel member of the snake-venom L-amino-acid oxidase family. Its amino-acid sequence shows high homology to other members of this family. For L-leucine, the values of k(cat) and K(M) are 31.1 s(-1) and 0.25 mM, respectively. The molecular weight of AHP-LAAO is about 60.7 kDa as determined by MALDI-TOF mass spectrometry. AHP-LAAO can also induce apoptosis of cultured Hela cells. Two sets of diffraction data with similar resolution limits (about 2.5 A) were collected independently at MacCHESS (Cornell High Energy Synchrotron Source, USA) and IHEP (Institute of High Energy Physics, Beijing, China). The crystals belong to space group I2(1)3, with unit-cell parameter a = 169.31 A, corresponding to one molecule in the asymmetric unit and a volume-to-weight ratio of 3.33 A(3) Da(-1). The final structural model is similar to that of L-amino-acid oxidase from Calloselasma rhodostoma venom.

Amino Acid Oxidoreductases↗

[An association of apolipoprotein B with pulse pressure in Chinese pedigrees with familial combined hyperlipidemia].

OBJECTIVE: To investigate the influencing factors of blood pressure phenotypes and the distribution of FDH in FCHL families. METHODS: Forty-two FCHL families with 435 members, 147 consanguine members and 90 members without consanguinity from Beijing area were studied. Eleven of the 42 FCHL families (26.2%) were identified as families with FDH syndrome. Stepwise regression analysis was used to analyze the association between the target variables and blood pressure phenotypes, such as systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP), of the 237 FCHL members aged 30 to 60 years. RESULTS: The prevalence of dyslipidemic hypertension in the FCHL relatives was significantly higher than that in the spouses (29.9% versus 8.9%, P < 0.01), with an odds ratio of 3.37 (95% CI 1.44 to 8.14). In the FCHL families body mass index (BMI), age and blood sugar were independent contributors to SBP, DBP, and MAP, respectively (all P < 0.05). Age and apolipoprotein B (apoB) were important contributors to pulse pressure (both P < 0.05). CONCLUSIONS: BMI and glucose are significant contributors to different phenotypes of blood pressure. Moreover, apoB is a significant contributor to pulse pressure in FCHL families.

Adult↗

Crystallographic snapshots of Aspergillus fumigatus phytase, revealing its enzymatic dynamics.

Understanding of the atomic movements involved in an enzymatic reaction needs structural information on the active and inactive native enzyme molecules and on the enzyme-substrate, enzyme-intermediate, and enzyme-product(s) complexes. By using the X-ray crystallographic method, four crystal structures of Aspergillus fumigatus phytase were obtained at resolution higher than 1.7 A. The pH-dependent catalytic activity of A. fumigatus phytase was linked to three water molecules that may prevent the substrate from binding and thus block nucleophilic attack of the catalytic imidazole nitrogen. Comparison of various structures also identified the water molecule that attacks the phosphamide bond during the hydrolysis process, and established the hydrolysis pathway of the intermediate. Additionally, two reaction product phosphates were observed at the active site, suggesting a possible product release pathway after hydrolysis of the intermediate. These results can help explain the catalytic mechanism throughout the whole acid phosphatase family, as all key residues are conserved.

6-Phytase↗

[Delivery after cryopreservation of percutaneous epididymal sperm aspiration specimens and intracytoplasmic sperm injection: 1 case report].

Intracytoplasmic sperm injection (ICSI) with sperm collected by percutaneous epididymal sperm aspiration (PESA) technique is nowadays the main treatment for obstructive azoospermia(OAS). To cryopreserve the epididymal sperm obstained by PESA can avoid repeat retrievals. We transferred the embryos fertilized by ICSI with frozen/thawed epididymal sperm and achieved a delivery, which shows that epididymal sperm obstained by PESA can be successfully cryopreserved.

Adult↗

[Modulation effects of recombinant human growth hormone on postburn hypermetabolism in burn patients].

OBJECTIVE: To explore the effects of recombinant human growth hormone (rhGH) on postuburn hypermetabolism in burn patients and its mechanism. METHODS: Thirty-two patients inflicted with burn of 50% to 90% TBSA admitted to our department during past 5 years (1998-2002) were enrolled in the study and randomly divided into A (with 0.25 U.kg(-1).d(-1) of rhGH treatment on 7-10 PBD, n=16) and B (with 0.25 U.kg(-1).d(-1) of normal saline as control, n = 16) groups. The changes in the rest energy expenditure (REE), non-protein respiratory quotient (NPRQ), glucose metabolism, nitrogen balance as well as plasma levels of endocrines and inflammatory mediators were determined before and after the administration of rhGH. RESULTS: rhGH was given to patients in group A during 7 - 10 PBD. The NPRQ in group A began to increase at the 7th PBD, raised to 0.80 +/- 0.09 in the 21st PBD. The plasma levels of PGE2, TXB2, TNF-alpha and IL-6 significantly decreased and insulin, rhGH and IGF-1 obviously increased when compared with those in group B. The accumulated nitrogen loss in group A was also much lower than that in group B. The plasma levels of adrenaline, cortisol, glucagon in group A were significantly higher than those in group B (P < 0.05). CONCLUSION: The postburn administration of rhGH timely could regulate postburn hypermetabolism in severely burned patients by increasing the plasma levels of GH, IGF-1 and insulin, which was beneficial to the improvement of nutrition state and to the promotion of protein synthesis and wound healing.

Adolescent↗

[Microorganism contamination in in vitro fertilization-embryo transfer system and their sources].

OBJECTIVE: To investigate the incidence of microorganism contamination in in vitro fertilization-embryo transfer (IVF-ET) and to determine the sources of microorganism. METHODS: Two thousand one hundred and seventy-four cycles of in vitro fertilization from January 1999 to June 2003 were evaluated retrospectively and bacterial cultures were performed in 61 semen samples from asymptomatic men with normal semen parameters and in 34 follicle fluid samples from infertility women through oocyte picking up procedures. RESULTS: Microorganisms were found in 11 cases. The incidence of their contamination in IVF culture system was 0.51% and the most common microorganisms were Escherichia coli and fungi. Microorganisms were detected in 97% of unprocessed semen, 10% in processed semen, 6% in semen mixed with media and 9% in follicle fluid. CONCLUSIONS: The incidence of microorganism contamination was 0.51% and the most common microorganisms were Escherichia coli and fungi. Semen may have the potential to contaminate IVF culture system.

Embryo Transfer↗

[Synthesis and antitumor activities of 10-hydroxy camptothecin derivatives].

AIM: To find new anticancer drug based on the structure of 10-hydroxy camptothecin. METHODS: Seven camptothecin derivatives (3 -9) were synthesized and the antitumor activities of these derivatives were evaluated. RESULTS: Structures of seven new compounds were determined by 1HNMR, IR, MS. Seven compounds showed inhibitory effects on Hela, BEL-7402, 7901 cell lines in vitro. Especially, compound 4 showed high bioactivities to all of the tumor cells in vitro, its anticancer activity against human cervical carcinoma Hela was much higher than that of 10-hydroxy camptothecin. CONCLUSION: Some compounds are worth further studying.

Antineoplastic Agents↗

Purification, partial characterization and crystallization of acucetin, a protein containing both disintegrin-like and cysteine-rich domains released by auto-proteolysis of a P-III-type metalloproteinase AaH-IV from Agkistrodon acutus venom.

AaH-IV, a P-III-type metalloproteinase found in Agkistrodon acutus venom, readily cleaves itself to release a stable protein named acucetin at 310 K under neutral and weakly alkaline conditions. A partial amino-acid residue sequence of acucetin indicates that the protein has a high homology to snake-venom proteins containing both disintegrin-like and cysteine-rich domains. Acucetin has been crystallized in space group R32, with hexagonal unit-cell parameters a = b = 155.98, c = 76.07 A. The V(M) value of about 2.97 A(3) Da(-1) suggests the presence of only one molecule in the asymmetric unit.

Agkistrodon↗