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1.
Biochem Biophys Res Commun ; 663: 8-15, 2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37116395

RESUMO

Helicobacter pylori is a bacterium that causes gastritis, peptic ulcer disease and adenocarcinoma while infecting human stomach. In the stomach H. pylori is under stresses caused by reactive oxygen and nitrogen species from host immune response, which causes oxidative DNA damage. The DNA damage in single base is repaired by base excision repair (BER) and/or nucleotide incision repair (NIR) pathways. H. pylori retains a minimal set of enzymes involved in the BER and NIR pathways. The HP1526 protein is a single apurinic/apyrimidinic (AP) endonuclease homologous to E. coli Xth protein but little is known for its structure up to now. In this study, the structure of the recombinant HP1526 protein from H. pylori (HpXthA) has been determined at a high resolution of 1.84 Å. From the structural analysis the HpXthA was found to belong to the Xth-like AP endonuclease family carrying the common fold of a central bilayer ß-sheet flanked by α-helices with a divalent metal ion bound. A Mn2+ ion and a 1,3-butanediol were unusually found and modeled around the active site. Structural and sequence comparisons among the AP endonucleases show well-conserved residues for metal and DNA binding and for catalysis. Interestingly, the presence of a small polar residue Ser201 of the HpXthA commonly found in NIR-proficient AP endonucleases instead of an aspartate residue in NIR-deficient enzymes suggests that the HpXthA retain a nucleotide incision repair activity.


Assuntos
DNA Liase (Sítios Apurínicos ou Apirimidínicos) , Helicobacter pylori , Humanos , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Helicobacter pylori/metabolismo , Escherichia coli/metabolismo , Dano ao DNA , Reparo do DNA , Nucleotídeos , Endonucleases/metabolismo
2.
Acta Crystallogr F Struct Biol Commun ; 75(Pt 7): 480-488, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31282867

RESUMO

The iron superoxide dismutase found in the pathogenic amoeba Acanthamoeba castellanii (AcFeSOD) may play essential roles in the survival of the parasite, not only by protecting it from endogenous oxidative stress but also by detoxifying oxidative killing of the parasite by host immune effector cells. The AcFeSOD protein was expressed in a stable form using an Escherichia coli expression system and was crystallized by the microbatch and hanging-drop vapour-diffusion methods. The structure was determined to 2.33 Šresolution from a single AcFeSOD crystal. The crystal belonged to the hexagonal space group P61 and contained 12 molecules forming three tetramers in the asymmetric unit, with an iron ion bound in each molecule. Structural comparisons and sequence alignment of AcFeSOD with other FeSODs showed a well conserved overall fold and conserved active-site residues with subtle differences.


Assuntos
Acanthamoeba castellanii/enzimologia , Superóxido Dismutase/química , Sequência de Aminoácidos , Domínio Catalítico , Cristalização , Cristalografia por Raios X , Multimerização Proteica , Estrutura Secundária de Proteína
3.
Urol Oncol ; 28(6): 673-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21062650

RESUMO

BACKGROUND: Although prostate cancer (CaP) is the most common male cancer in developed countries, the incidence of CaP in Vietnam remains unknown and the patients often seek treatment at a late stage in their illness. The mass screening of CaP, which has been performed since Jan 2008 in Binh Dan hospital (Ho Chi Minh City) aims to evaluate the effect of CaP mass screening in Vietnam. The details of CaP treatment from 1999 to now in Ho Chi Minh City (HCMC) were also used for evaluation and comparison. MATERIALS AND METHODS: From the first quarter of 2008, we started a free CaP screening program in HCMC. There were 408 cases during first round of results. When inspecting CaP treatment, all papers and studies of CaP at Binh Dan hospital from 1999 were analyzed, including 1,775 CaPs treated. RESULTS AND DISCUSSIONS: A total of 408 subjects were screened during the CaP program. Prostate biopsies were carried out on 87 men (21.3%) based on PSA values and DRE results. Ten of these biopsied men (2.5%) were diagnosed with CaP, mostly with Gleason's scores of 5 to 7 and in an early clinical stage. In reviewing CaP treatment from 1999 to 2009, complete androgen blockade/maximal androgen blockade (MAB/CAB) was widely used, while chemotherapy and radiotherapy were not routinely used. Open and laparoscopic total prostatectomy remarkably increased due to the many efforts of CaP screening. The number of CaP cases has now reached and overtaken the number of bladder cancer cases in our hospital. Similarly, early diagnosis rates have increased in parallel with radical treatment. CONCLUSION: Our initial outcomes reflected a low prevalence of CaP in general (2,5%), but a high occurrence of medium grade lesions (Gleason 7) among patients who tested positive for CaP. On one hand, this observation highlights the value of the CaP screening programs in alerting doctors/people and detecting more cases in the early stages of development. On the other hand, the benefit of a mass screening program for CaP is not proven. Meanwhile, selective CaP screening takes advantage of diagnosis and treatment in our country.


Assuntos
Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Detecção Precoce de Câncer/estatística & dados numéricos , Humanos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Prevalência , Vietnã/epidemiologia
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