The Wish List: Articulating and Responding to New Teachers\u27 Concerns

Although it is possible to cite general trends about the concerns of beginning teachers, each beginner will have specific needs and questions. Clearly, mentoring matters, and mentors are especially helpful when they recognize and attend to the beginners\u27 specific needs. Here, ErinnvBentley describes a Wish List she developed as a novice teacher which she used as a method for clearly and specifically documenting skills she wanted to learn. This list contained both general teaching skills and those particular to her teaching context. Throughout her first years in the classroom she used the Wish List as a personal professional development guide: continually referring to the list, adding new skills or concepts, and systematically looking for mentors for guidance. (Contains 1 figure.

The Substrate Capture Mechanism of <i>Mycobacterium tuberculosis</i> Anthranilate Phosphoribosyltransferase Provides a Mode for Inhibition

Anthranilate phosphoribosyltransferase (AnPRT, EC 2.4.2.18) is a homodimeric enzyme that catalyzes the reaction between 5′-phosphoribosyl 1′-pyrophosphate (PRPP) and anthranilate, as part of the tryptophan biosynthesis pathway. Here we present the results of the first chemical screen for inhibitors against <i>Mycobacterium tuberculosis</i> AnPRT (<i>Mtb</i>-AnPRT), along with crystal structures of <i>Mtb</i>-AnPRT in complex with PRPP and several inhibitors. Previous work revealed that PRPP is bound at the base of a deep cleft in <i>Mtb</i>-AnPRT and predicted two anthranilate binding sites along the tunnel leading to the PRPP binding site. Unexpectedly, the inhibitors presented here almost exclusively bound at the entrance of the tunnel, in the presumed noncatalytic anthranilate binding site, previously hypothesized to have a role in substrate capture. The potencies of the inhibitors were measured, yielding <i>K</i>_i values of 1.5–119 μM, with the strongest inhibition displayed by a bianthranilate compound that makes hydrogen bond and salt bridge contacts with <i>Mtb</i>-AnPRT via its carboxyl groups. Our results reveal how the substrate capture mechanism of AnPRT can be exploited to inhibit the enzyme’s activity and provide a scaffold for the design of improved <i>Mtb</i>-AnPRT inhibitors that may ultimately form the basis of new antituberculosis drugs with a novel mode of action