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Summaries of Recent Publications by HWI Scientists
 
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Using crystallization technology and the grocery store as a teaching tool
What do milk, hand sanitizer, multivitamins and aspirin have in common? Surprisingly, the answer is that, under certain circumstances, they all can be used to promote protein crystallization.

A few years ago, researchers in California found that screening a protein sample in the presence of many different small molecules often reveals good crystal growth conditions for the protein of interest.  Small molecules that facilitate crystal growth are termed “silver bullets”.  HWI scientists Eddie Snell and Joe Luft reasoned that common products found on grocery store shelves might serve as inexpensive and effective “pseudo-silver bullets” (PSBs).  This turns out to be true and, not only that, "grocery store crystallography" is proving to be a great way to introduce students to scientific methods. [Learn more]

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Bacterial iron acquisition and antibiotic development
The Gulick lab has published a manuscript in the journal “Biochemistry” that describes the atomic structure of a bacterial protein, BasE, that is involved in iron acquisition in the bacteria, Acinetobacter baumannii. The paper also describes how this protein recognizes a new inhibitor (a small chemical that blocks its activity) that was identified in the lab of Gulick’s collaborator, Dr. Courtney Aldrich of the Center for Drug Design, University of Minnesota. This paper is part of an on-going collaboration to identify compounds that can be developed into antibiotics. Also working with Gulick and Aldrich were Eric Drake, at HWI, and Ben Duckworth and Joao Neres, at the University of Minnesota.  [Learn more]

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The role of capsular polysaccharides in bacterial pathogenesis
The Schulz and Umland labs collaborated with the Russo and Campagnari labs at UB in the first study to address the role of capsule in the pathogenesis of A. baumannii infection. A. baumannii infection is an increasing problem in health care settings, especially multi-drug resistant strains. Capsule is a protective polysaccharide coating present on many bacterial species. Its composition is highly variable, even across different strains of the same bacteria. Differences in capsule composition alter virulence levels and immune responses between strains, and thus can be important in the vaccine development. Our results demonstrated that the presence of A. baumannii capsule was essential for the growth and survival of the bacteria in a infection model. Further, we identified two proteins involved in capsule synthesis, PTK and EpsA, as new antibacterial drug targets that may be useful against multi-drug resistant strains of A. baumannii. [Learn more]

A gramicidin D-NaI complex: Insight into preferred transport
Proper salt balance is critical to health, and hypertension is associated with sodium/potassium salt balance.  Gramicidin D is a naturally occurring antibiotic that forms channels that transport sodium and potassium ions through biological membranes.  It has the unusual property of favoring the transport of sodium ions.

HWI scientist, Dr. William Duax, and his colleagues at the Technical University of Lodz in Poland, have recently determined the first crystal structure of a gramicidin-sodium complex.  This structure provides insight into the basis for preferred sodium transport. [Learn more]
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Structural basis of substrate binding to COX-2
The Malkowski lab has published a manuscript in the Journal of Biological Chemistry that describes the molecular basis behind the binding of the omega-6 and omega-3 fatty acids arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) to Cyclooxygenase-2 (COX-2). Through the metabolism of these polyunsaturated fatty acids, COX-2 produces unique signaling molecules that exert a wide range of biological effects related to inflammation, fever, and pain. Department of Structural Biology graduate students Alex Vecchio and Danielle Simmons made significant contributions to this research. [Learn more]

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A bacterial enzyme with an unusual catalytic center
The short-chain oxidoreductase (SCOR) enzyme family is large (20,000+ members) and highly diverse, participating in many important metabolic pathways. The Duax and Umland labs worked together to identify and determine the structure of an unusual member of the SCOR family, Q9HYA2, from the pathogenic bacteria Pseudomonas aeruginosa. This protein possesses an atypical catalytic site. Further analysis of this protein indicated that analogous enzymes are present in 27 additional bacterial species, the majority of which are also human pathogens (e.g., A. baumannii, K. pneumoniae). HWI scientists have a long-standing interest in exploring the evolutionary diversity of this important enzyme family, with the results impacting infectious disease, cancer, and human development. [Learn more]

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