CRYSTALLOGRAPHIC STRUCT FUNCTION STUDIES OF MOESIN, CELLULASES, & FLAVOENZYMES

我们正在与药物化学家合作设计药物的抑制剂 临床上很麻烦的细菌-内酰胺酶，它提供了 对青霉素类和头孢菌素类耐药。通过在低温下工作 温度，我们希望稳定和可视化反应 抑制途径中的中间体。四-内酰胺类化合物 阴沟肠杆菌(P99)和阴沟肠杆菌(Gc1)产C-内酰胺酶 在光束线A1上用2K普林斯顿探测器在100-K下进行检查 入库模式。氨曲南和氨苄西林与Gc1络合 酶，潜在的抑制剂KM233和DVR3与 P99酶。P99和Gc1复合体给出的数据约为2.7 和2.3分辨率分别为。初始阶段化将基于 已知的天然结构。GC1建筑群的地图现在正在制作中 检查过了。质粒载体介导的SHV A类新晶体 -内酰胺酶特性。小晶体(25x75微米) 衍射率为2.4决议。解析不佳的倒数间距 在普林斯顿的探测器上，估计有250个-1，已阻碍 由Denzo编制索引，以便将使用XGEN。因为在那里 每个不对称单位至少有4个拷贝的分子，我们 可能不会继续使用这种晶体形式。在剩下的时间里，新的 提供万古霉素的氨基酸连接酶VanB的50微米晶体 对肠球菌的抵抗力，迅速进行了表征，以便计划 用于将来的工作，并被发现衍射率约为4，对于一个 85x83x83的单斜晶格和=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-.