Tetradehydrocheilanthiofolinium

21926168

Protein glutaminase, which converts a protein glutamine residue to a glutamate residue, is expected to be useful as a new food-processing enzyme. The crystal structures of the mature and pro forms of the enzyme were refined at 1.15 and 1.73 a resolution, respectively. The overall structure of the mature enzyme has a weak homology to the core domain of human transglutaminase-2. The catalytic triad (Cys-His-Asp) common to transglutaminases and cysteine proteases is located in the bottom of the active site pocket. The structure of the recombinant pro form shows that a short loop between S2 and S3 in the proregion covers and interacts with the active site of the mature region, mimicking the protein substrate of the enzyme. Ala-47 is located just above the pocket of the active site. Two mutant structures (A47Q-1 and A47Q-2) refined at 1.5 a resolution were found to correspond to the enzyme-substrate complex and an S-acyl intermediate. Based on these structures, the catalytic mechanism of protein glutaminase is proposed.

Enzyme Catalysis, Enzyme Mechanisms, Enzyme Mutation, Enzyme Structure, X-ray Crystallography, Covalent Intermediate, Cysteine Protease, Proenzyme, Protein Glutaminase,

Crystal Structures of Protein Glutaminase and Its Pro Forms Converted into Enzyme-Substrate Complex*An external file that holds a picture, illustration, etc. Object name is sbox.jpg

Ryota Hashizume,‡ Yukiko Maki,‡ Kimihiko Mizutani,‡ Nobuyuki Takahashi,‡ Hiroyuki Matsubara,§ Akiko Sugita,§ Kimihiko Sato,§ Shotaro Yamaguchi,§ and Bunzo Mikami‡,1

2011 Nov 4

29659909

Background
Human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV2) are strongly associated, although mechanisms are not fully understood. An HIV prevention trial allowed reexamination of this association at individual and community levels.

Methods
The HIV Prevention Trials Network 071 (PopART) study evaluates a combination prevention intervention in 21 urban communities in Zambia and South Africa. To measure impact on HIV infection incidence, a cohort of approximately 2000 adults (age range, 18-44 years) was selected randomly from each community. Baseline data on sociodemographic characteristics, behavior, and HIV/HSV2 serologic findings were used to examine the association between HIV and HSV2. At the community level, HIV prevalence was plotted against HSV2 prevalence.

Results
A total of 38691 adults participated. HSV2 prevalence among women and men was 50% and 22%, respectively, in Zambia and 60% and 27%, respectively, in South Africa. Estimated HSV2 infection incidence among those aged 18-24 years was 8.06 cases/100 person-years (95% confidence interval [CI], 6.76-9.35) and 1.76 cases/100 person-years (95% CI, 1.30-2.22) among women and men, respectively. A 6-fold higher odds of HIV infection was seen in HSV2-infected individuals in both sexes, after adjustment for confounders (odds ratio, 6.66 [95% CI, 6.07-7.31] among women and 6.57 [95% CI, 5.56-7.77] among men). At the community-level, there was a strong linear relationship between HIV and HSV2 prevalence (ρ = 0.92; P < .001). Conclusions There was an exquisite association between these 2 infections, at the individual and community levels, likely due in part to a powerful cofactor effect of HSV2 on HIV transmission. HSV2 control could contribute to HIV prevention.

HIV, HSV2, South Africa, Zambia, cofactor, urban, ecological analysis

Sexually Transmitted Bedfellows: Exquisite Association Between HIV and Herpes Simplex Virus Type 2 in 21 Communities in Southern Africa in the HIV Prevention Trials Network 071 (PopART) Study

John Bradley,1 Sian Floyd,1 Estelle Piwowar-Manning,4 Oliver Laeyendecker,5 Alicia Young,6 Nomtha Bell-Mandla,7 Justin Bwalya,8 Peter Bock,7 Sarah Fidler,3 Helen Ayles,2,8 Richard J Hayes,1 and HPTN 071 (PopART) Study Team

2018 Aug 1;