Heme proteins of the protozoan parasite Giardia intestinalis

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Heme is a biomolecular tool whose purpose depends on the protein that wields it. Its most famous role is as the oxygen-binding site in hemoglobin of our red blood cells. However, heme has many other roles as well, and for most organisms it is indispensable. Until recently, the protozoan parasite Giardia intestinalis was thought to be one of the rare organisms that did not need heme, as it lacked key enzymes that require this cofactor. However, the genome of Giardia intestinalis has genes for several heme proteins: a flavohemoglobin and four members of the cytochrome b5 family of electron transfer proteins. Both sets of proteins have unusual features that are not found in other family members. Flavohemoglobins are found in bacteria and fungi where they protect the microbe from nitric oxide by converting it to harmless nitrate. The Giardia protein likely has the same role, but its amino acid sequence is larger due to inserts within the heme-binding globin domain and the flavoprotein domain. We are interested in what this difference, and others within the heme-binding site, may have on the functional properties of Giardia protein, and whether these differences could lead to the design of agents that inhibit the Giardia protein without affecting the flavohemoglobin of benign microorganisms that are also found in the gut. The Giardia cytochromes b5 are also interesting because they lack features commonly associated with other family members, yet have other features that are unique to them. They are also found within the cell in locations not typically associated with cytochromes b5, and they have no known function. We suspect that the differences that the Giardia cytochromes exhibit are connected to their as-yet undiscovered functions, and we are trying to understand this connection by examining the properties of the Giardia cytochromes and altered versions that we have prepared. Finally, we are searching for additional heme proteins that may have escaped easy identification because they are so distantly related to their relatives. With our work we will have a fuller understanding of the biochemistry of an important human and animal pathogen, and potentially reveal new biochemical pathways and processes for other researchers to follow.