Milton H. Saier, Jr.
University of California at San Diego, USA
Milton Saier has broad interests in molecular biology. He directs the research in two laboratories, one a bioinformatics laboratory, and the other a molecular genetics/biochemistry lab. His interests deal with mechanisms and evolution of transport protein functions and genomic analyses of transport systems in microorganisms (dry lab). In the wet lab, mechanisms of transcriptional and enzyme activity regulation are the focus of their research. His current efforts deal with insertion sequence-mediated directed mutation control by DNA configuration and DNA binding proteins in E. coli. The present abstract results from efforts of himself and his research associate, Dr. Zhongge Zhang, as well as others. Recent efforts in the biochemistry section of the lab have revealed a novel mechanism of global regulation of carbon and energy metabolism. Saier has published over 700 articles over the past 40 years on a wide range of subjects including molecular biological and environmental topics.
Our laboratory maintains and curates the Transporter Classification Database (TCDB, www.tcdb.org), which is continually updated and expanded, and currently includes over 11,000 transport systems, 1000 families and 64 superfamilies, citing over 12,500 references. We have developed software that allow us to identify distant relationships between proteins using the Transitivity Rule with results confirmed by sequence motif similarities, Pfam assignments, common evolutionary pathways and 3-D structural comparisons. Many superfamilies contain proteins of only one mechanistic type (i.e., channel proteins, secondary carriers, primary active transporters or group transporters (TC classes 1-4, respectively)). However, our recent analyses show that some superfamilies include multiple protein functional types. For example, the Transporter/Opsin/G-protein (TOG) superfamily includes channels, carriers, primary active transporters and receptors, but, no enzymes. Another superfamily, the 4 TMS junctional complex (4JC) superfamily includes gap and tight junctional complex proteins, simple channels and channel auxiliary proteins, but no carriers or primary active transporters. The Major Facilitator Superfamily (MFS) consists largely of secondary carriers, lacks channel proteins, but includes transmembrane domains in P-type ATPases, integral membrane proteases, glycosyltransferases and tRNA synthases. In some cases we could show that within a single superfamily, 3-D structures can vary so much that their common features become unrecognizable, even though primary sequence similarity is appreciable. These experimental approaches will be discussed and compared.