Ph.D. Harvard University (1966)
Office: Remsen 309
Phone: (718) 997-4132
FAX: (718) 997-5531
E-mail: burton.tropp@qc.cuny.edu
We are currently investigating the function of the amino terminal region of bacterial cardiolipin (CL) synthase, a membrane-bound enzyme that catalyzes CL formation by transferring a phosphatidyl group from one phosphatidylglycerol molecule to another.
CL synthase belongs to the PLD superfamily of enzymes, which also includes phospholipase D, endonucleases, phosphatidylserine synthase, poxvirus envelope proteins, and Yersinia murine toxin (Ymt). All members of the superfamily have at least one copy of the HKD motif, which has the sequence HXK(X)4D (where X is any amino acid). However, most members including CL synthase have two copies of the HKD motif. The sequence of the bacterial gene that codes for CL synthase, cls, was first determined for Escherichia coli and later for many other bacteria. Bacterial cls genes share several sequence motifs that are not present in other PLD family members. Twenty two of these conserved residues are located within the first 80 residues.
1 MTTVYTLVSW LAILGYWLLI AGVTLRILMK RRAVPSAMAW
41 LLIIYILPLV GIIAYLAVGE LHLGKRRAER ARAMWPSTAK
The first 80 amino acid residues in E. coli CL synthase. Residues conserved in CL synthases from 19 different bacterial species are shown in white letters in a black background.
The fact that these conserved residues are present in a wide variety of gram-positive and gram-negative bacteria is somewhat surprising because the mature bacterial enzyme appears to be missing ~80 residues from its N-terminus and a mutant E. coli CL synthase lacking residues 2-60 can still catalyze CL formation. It therefore seems reasonable to conclude that the N-terminus does not contribute to the mature enzyme’s catalytic activity. If this conclusion is correct, then what is the function of the N-terminus and why are 22 N-terminal residues conserved in widely different bacterial species? We are currently testing the hypothesis that at least some of the conserved residues function as a signal that directs specific cleavage of the N-terminus from the rest of the polypeptide. This cleavage may be part of a post-translational process that directs the mature CL synthase to its ultimate site in the cell membrane. At a fundamental level, the discovery of a new mechanism for processing bacterial membrane proteins would advance our understanding of how bacterial proteins are directed to specific membrane sites and at a practical level, it might provide a novel target for drugs that block bacterial cell growth.
Representative Publications:
1. Guo D. G and B. E. Tropp “A second Escherichia coli protein with CL synthase activity.” Biochim Biophys Acta 1483:2 263-74 (2000).
2. Tropp, B. E., "Cardiolipin synthase from Escherichia coli." Biochim. Biophys. Acta 1348: 192-200 (1997).
3. Guo, D. G. and B. E. Tropp, "Cloning of the B. firmus OF4 cls gene and characterization of its gene product." Biochim. Biophys. Acta 1389: 34-42 (1997).
Book:
Tropp, B. E. “Molecular Biology: Genes to Proteins” Jones and Bartlett (2008)