CRYSTALLOGRAPHIC STRUCT FUNCTION STUDIES OF MOESIN, CELLULASES, & FLAVOENZYMES

我们正在与药物化学家合作， 临床上棘手的细菌 - 内酰胺酶，其提供 对青霉素和头孢菌素的耐药性。 在低温实验室工作 我们希望稳定和可视化反应 抑制途径中的中间体。 四 - 内酰胺络合物 两个C级 来自阴沟肠杆菌的β-内酰胺酶（P99和GC 1）是 在100-K下用2k Princeton探测器在光束线A1上进行检查， binned模式。 氨曲南和氨苄青霉素与GC 1络合， 酶和潜在的抑制剂KM 233和DVR 3与 P99酶 P99和GC 1复合物的数据约为2.7
和2.3
决议，分别。 初始阶段将基于 已知的原生结构。 GC 1复合体的地图现在正在 考察 质粒介导的A类SHV的新晶体 β-内酰胺酶进行了表征。 小晶体（25 x75微米） 衍射至2.4
分辨率 一个很难分辨的倒数间距 在普林斯顿探测器上，估计大约有250个
1、阻碍 由DENZO索引，以便使用XGEN代替。 因为 每个不对称单位至少有4个分子拷贝，我们 不能继续使用这种晶体形式。 在剩下的时间里，新 50微米的vanB晶体，一种提供万古霉素的氨基酸连接酶 对肠球菌的耐药性，迅速进行了表征，以便计划 为未来的工作，并发现，
，对于 85 x83 x83单斜晶胞
和 =99-。

We are working with medicinal chemists to design inhibitors of clinically-troublesome bacterial -lactamases, which provide resistance to penicillins and cephalosporins. By working at cryogenic temperatures, we hope to stabilize and visualize reaction intermediates in the inhibition pathway. Four -lactam complexes of two class C -lactamases from Enterobacter cloacae (P99 and GC1) were examined at 100-K on beamline A1 with the 2k Princeton detector in binned mode. Aztreonam and ampicillin were complexed with the GC1 enzyme, and potential inhibitors KM233 and DVR3 were complexed with the P99 enzyme. The P99 and GC1 complexes gave data to about 2.7
and 2.3
resolution, respectively. Initial phasing will be based on the known native structures. Maps of the GC1 complexes are now being examined. New crystals of the plasmid-mediated SHV class A -lactamase were characterized. The small crystals (25x75 microns) diffracted to 2.4
resolution. A poorly resolved reciprocal spacing on the Princeton detector, estimated to be about 250
-1, has hindered indexing by DENZO so that XGEN will be used instead. Because there appear to at least 4 copies of the molecule per asymmetric unit, we may not continue to use this crystal form. In the remaining time, new 50 micron crystals of vanB, an aminoacid ligase providing vancomycin resistance to enterococci, were quickly characterized in order to plan for future work and were found to diffract to about 4
, for a monoclinic cell with 85x83x83
and =99-.