Structural requirements for recognition of essential porphyrin byPorphyromonas gingivalis

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Porphyromonas gingivalis is an anaerobic Gram negative bacterium implicated in destructive infection of the tissues that support the teeth. This organism is unusual in that it cannot synthesize the porphyrin macrocycle and is therefore dependent on exogenous porphyrin for growth. Accordingly, in addition to physiologically relevant sources of heme, growth is stimulated by a number of iron-free porphyrins. Without exception, the capacity of porphyrins to support normal growth of P. gingivalis was associated with recognition by a sub-domain protein HA2 which is located within three outer-membrane proteins and which recognizes the porphyrin macrocycle in an iron-independent manner. Previous analysis in our laboratories indicated that recognition of the propanoate face of porphyrin was a distinguishing feature of the HA2 receptor. More detailed analysis indicated that derivatization of the two propionic acid substituents as their methyl esters or taurine derived N-(ethyl-2-sulfonic acid)amides abolished recognition by HA2 whereas the ethylenediamine derived N-(2-aminoethyl)amides did not affect binding by HA2 . The importance of the 2- and 4-vinyl groups of protoporphyrin IX for transport and growth was evaluated by testing compounds with hydrogen, sulfonic acid and glycol substituents at the 2- and 4-positions. While these derivatives bound HA2 with high affinity, study of protoporphyrin isomers indicated that the distribution of vinyl group substitution was important in regulating recognition by HA2 . In this report, the behaviour of mesoporphyrin IX in which the vinyl groups are replaced by ethyl groups and of chlorin E4 which contains only one propionic acid sidechain, were investigated to further define the structural requirements for recognition by HA2 . Both porphyrins were recognized by low affinity interactions. Based on these findings, a model for binding is proposed. The apparently unique mode of recognition of porphyrins by the receptor presents opportunities for specific targeting of this pathogenic organism.