Mechanism of chorismate dehydratase MqnA, the first enzyme of the futalosine pathway, proceeds via substrate-assisted catalysis.

MqnA, the only chorismate dehydratase known so far, catalyzes the initial step in the biosynthesis of menaquinone via the futalosine pathway. Details of the MqnA reaction mechanism remain unclear. Here, we present crystal structures of Streptomyces coelicolor MqnA and its active site mutants in complex with chorismate and the product 3-enolpyruvyl-benzoate, produced during heterologous expression in Escherichia coli. Together with activity studies, our data are in line with dehydration proceeding via substrate assisted catalysis, with the enol pyruvyl group of chorismate acting as catalytic base. Surprisingly, structures of the mutant Asn17Asp with copurified ligand suggest that the enzyme converts to a hydrolase by serendipitous positioning of the carboxyl group. All complex structures presented here exhibit a closed Venus flytrap fold, with the enzyme exploiting the characteristic ligand binding properties of the fold for specific substrate binding and catalysis. The conformational rearrangements that facilitate complete burial of substrate/product, with accompanying topological changes to the enzyme surface, could foster substrate channeling within the biosynthetic pathway.

Relationship of age and refraction to central corneal thickness.

PURPOSE: To obtain descriptive statistics of central corneal thickness (CCT) in a large population of normal eyes undergoing refractive surgery and study the relationship of 2 variables, age and refraction, with CCT. SETTING: Cornea and Laser Eye Institute, Hersh Vision Group, Teaneck, NJ. METHODS: The CCT of 5158 patients was measured using an ultrasound pachymeter. Age and preoperative spherical equivalent were recorded for all patients. The entire population and subgroups stratified to age and spherical equivalent were analyzed. RESULTS: Mean CCT was 544 µm with an SD of 34 µm and a range of 415-695 µm. CCT did not correlate with either age (r = 0.00645) or refraction (r = 0.00072). CONCLUSIONS: This study defines the CCT in a large population of patients undergoing refractive surgery. In this population, age and refraction did not affect CCT.

Vitreous hemorrhage as the initial manifestation of X-linked retinoschisis in a 9-month-old infant.

A 9-month-old infant presented with progressive esotropia, bilateral vitreous hemorrhages, bullous retinoschises, and peripheral retinal detachments. X-linked retinoschisis was diagnosed on the basis of electroretinogram findings. We report a case of vitreous hemorrhage as the initial presentation of X-linked retinoschisis in one of the youngest patients discussed in the literature.