Alkylhydroperoxidase D (AhpD)
Carboxymuconolactone decarboxylase: peroxidase activity (CMD) and no peroxidase activity (CMDn)
Hydrolase-CMD fusion with peroxidase activity (HCMD) and no peroxidase activity (HCMDn)
Double CMD with peroxidase activity (DCMD) and no peroxidase activity (DCMDn)
Other alkylhydroperoxidase with peroxidase activity (AlkyPrx) and no peroxidase activity (AlkyPrxn)
Carboxymuconolactone decarboxylase family.
Alkylhydroperoxidase AhpD core. The profiles do not make a distinction between the different families.
Alkylhydroperoxidase D: InterPro: IPR004675
AhpD core and IPR004674
Carboxymuconolactone decarboxylase: InterPro: IPR004675
Hydrolase-CMD fusion: Pfam: PF00561
alpha/beta hydrolase fold InterPro: IPR003089
Alpha/beta hydrolase; IPR000073
Alpha/beta hydrolase fold-1; IPR012790
3-oxoadipate enol-lactonase and IPR012788
4-carboxymuconolactone decarboxylase. Prosite: PR00111
Double CMD: InterPro: IPR004675
Other alkylhydroperoxidase: Pfam: PF07883
Cupin domain. InterPro: IPR013096
conserved barrel and IPR011051
Proteins from AhpD superfamily also called Carboxymuconolactone decarboxylase (CMD: EC:188.8.131.52) are involved in protocatechuate catabolism. They have no sequence identity with AhpC or other proteins but has alkylhydroperoxidase activity and possibly additional physiological activities. The proteins contain the following key motif for peroxidase activity: E[x]11CxHC[x]3H (Nunn et al., 2002).
MtuAhpD is a trimer in a symmetrical cloverleaf arrangement (Nunn et al., 2002). Each subunit exhibits a new all-helical protein fold in which the two catalytic sulfhydryl groups, Cys-130 and Cys-133, are located near a central cavity in the trimer. The structure supports a mechanism for the alkylhydroperoxidase activity in which Cys-133 is deprotonated by a distant glutamic acid via the relay action of His-137 and a water molecule. The cysteine then reacts with the peroxide to give a sulfenic acid that subsequently forms a disulfide bond with Cys-130. Based on sequence similarities and domains organisation, the four following families have been defined: carboxymuconolactone decarboxylase, hydrolase-CMD fusion, double CMD and other alkylhydroperoxidase.
Alkylhydroperoxidase D: typical AhpD proteins contain two CMD domains and the functional enzyme is composed by a trimer.
Carboxymuconolactone decarboxylase simple and double: the proteins contain one and two domains. "CxxC" motif is abscent from the second domain. The proteins are monomeric
Hydrolase-CMD fusion: In some bacteria a gene fusion event leads to expression of CMD with a hydrolase involved in the same pathway . In these bifunctional proteins, CMD represents the C-terminal domain, Abhydrolase_1 represents the N-terminal domain. The proteins form probably a hexamer althought no cristal has been obtained yet.
Other alkylhydroperoxidase: undefined proteins containing CMD domain fused to a second domain: mainly a cupin domain. In general manner, when part of the catalytic motif "CxxC" is missing from one sequence, this sequence has been considered to encode for a protein without peroxidase activity (namely with the small "n").
Nunn CM, Djordjevic S, Hillas PJ, Nishida CR, Ortiz de Montellano PR. The crystal structure of Mycobacterium tuberculosis alkylhydroperoxidase AhpD, a potential target for antitubercular drug design. J.Biol.Chem. 277: 20033-20040. PMID: 11914371
Ito K, Arai R, Fusatomi E, Kamo-Uchikubo T, Kawaguchi S, Akasaka R, Terada T, Kuramitsu S, Shirouzu,M. and Yokoyama S. Crystal structure of the conserved protein TTHA0727 from Thermus thermophilus HB8 at 1.9 A resolution: A CMD family member distinct from carboxymuconolactone decarboxylase (CMD) and AhpD. Protein Sci. 2006 May;15(5):1187-92. PMID: 16597838