Proceedings of the 10th International Colloquium on Paratuberculosis

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Atypical structural features <strong>of</strong> two MAP P60 family members
Kasra X Ramyar 1 , Cari K. Lingle 1 , William J. McWhorter 1 , Samuel Bouyain 1 , John P Bannantine 2 ,
Brian V Geisbrecht 1
1 University <strong>of</strong> Missouri Kansas City, USA; 2 National Animal Disease Center, USDA-ARS, Ames, Iowa, USA
The majority <strong>of</strong> Map gene products have no known function. In order to better understand <strong>the</strong> pathobiology
<strong>of</strong> this mycobacterium, we have begun to study <strong>the</strong> structure-function relationship <strong>of</strong> a subset <strong>of</strong> Map proteins.
We have selected a number <strong>of</strong> gene products unique to Map which are ei<strong>the</strong>r predicted to be secreted
or expressed on <strong>the</strong> surface <strong>of</strong> <strong>the</strong> mycobacterium. Here we report <strong>the</strong> atomic resolution crystal structures <strong>of</strong>
two Map proteins, 1272c and 1204. Both proteins are members <strong>of</strong> <strong>the</strong> NlpC/P60 superfamily <strong>of</strong> peptidylglycan
hydrolases and are predicted to be expressed on <strong>the</strong> surface <strong>of</strong> <strong>the</strong> bacteria. Surprisingly, nei<strong>the</strong>r protein
appears to have a functional catalytic core. It is clear from <strong>the</strong> structure <strong>of</strong> 1272c that <strong>the</strong> residues required
for hydrolysis are absent, strongly suggesting a role as a binding protein or receptor for this protein. While <strong>the</strong>
Cys-His-Glu catalytic triad is present in 1204, o<strong>the</strong>r residues occlude access to <strong>the</strong> catalytic site. Based on
<strong>the</strong>se two structures, and a thorough search <strong>of</strong> <strong>the</strong> Map genome, we can conclude that <strong>the</strong> canonical role <strong>of</strong>
a peptidylglycan hydrolase is not fulfilled by ei<strong>the</strong>r 1204 or 1272c. As both <strong>the</strong>se proteins are strongly recognized
by antibodies from infected animals, we propose that <strong>the</strong>y function in an as yet undetermined role during
pathogenesis.
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