ARD/ARD' family; The two acireductone dioxygenase enzymes (ARD and ARD', previously known as E-2 and E-2') from Klebsiella pneumoniae share the same amino acid sequence, but bind different metal ions: ARD binds Ni2+, ARD' binds Fe2+. ARD and ARD' can be experimentally interconverted by removal of the bound metal ion and reconstitution with the appropriate metal ion. The two enzymes share the same substrate, 1,2-dihydroxy-3-keto-5-(methylthio)pentene, but yield different products. ARD' yields the alpha-keto precursor of methionine (and formate), thus forming part of the ubiquitous methionine salvage pathway that converts 5'-methylthioadenosine (MTA) to methionine. This pathway is responsible for the tight control of the concentration of MTA, which is a powerful inhibitor of polyamine biosynthesis and transmethylation reactions. ARD yields methylthiopropanoate, carbon monoxide and formate, and thus prevents the conversion of MTA to methionine. The role of the ARD catalyzed reaction is unclear: methylthiopropanoate is cytotoxic, and carbon monoxide can activate guanylyl cyclase, leading to increased intracellular cGMP levels. This family also contains other members, whose functions are not well characterized.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 807045907   31 VCCSLDADKYENDPELEKIRRERNYSWMDII-TICKDKLPNYEEKIKMFYEEHLHLDDEIRYILDGSGYFDVRDKEDQWI 109
Cdd:pfam03079  36 LYWKLDADDEETAEDLLRILKYKHYDDVDIDvTVCPETTPNFDEKLEKFFEEHLHTDEEIRYIVEGTGYFDVRDKDDVWI 115

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 807045907  110 RIFMEKGDMVTLPAGIYHRFTVDEKNYTKAMRLFVGEPVWTA 151
Cdd:pfam03079 116 RVFVEKGDLISLPAGIYHRFTTTPDNYVKALRLFVTKPGWTA 157

ARD/ARD' family; The two acireductone dioxygenase enzymes (ARD and ARD', previously known as E-2 and E-2') from Klebsiella pneumoniae share the same amino acid sequence, but bind different metal ions: ARD binds Ni2+, ARD' binds Fe2+. ARD and ARD' can be experimentally interconverted by removal of the bound metal ion and reconstitution with the appropriate metal ion. The two enzymes share the same substrate, 1,2-dihydroxy-3-keto-5-(methylthio)pentene, but yield different products. ARD' yields the alpha-keto precursor of methionine (and formate), thus forming part of the ubiquitous methionine salvage pathway that converts 5'-methylthioadenosine (MTA) to methionine. This pathway is responsible for the tight control of the concentration of MTA, which is a powerful inhibitor of polyamine biosynthesis and transmethylation reactions. ARD yields methylthiopropanoate, carbon monoxide and formate, and thus prevents the conversion of MTA to methionine. The role of the ARD catalyzed reaction is unclear: methylthiopropanoate is cytotoxic, and carbon monoxide can activate guanylyl cyclase, leading to increased intracellular cGMP levels. This family also contains other members, whose functions are not well characterized.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 807045907   31 VCCSLDADKYENDPELEKIRRERNYSWMDII-TICKDKLPNYEEKIKMFYEEHLHLDDEIRYILDGSGYFDVRDKEDQWI 109
Cdd:pfam03079  36 LYWKLDADDEETAEDLLRILKYKHYDDVDIDvTVCPETTPNFDEKLEKFFEEHLHTDEEIRYIVEGTGYFDVRDKDDVWI 115

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 807045907  110 RIFMEKGDMVTLPAGIYHRFTVDEKNYTKAMRLFVGEPVWTA 151
Cdd:pfam03079 116 RVFVEKGDLISLPAGIYHRFTTTPDNYVKALRLFVTKPGWTA 157

Cupin domain; This family represents the conserved barrel domain of the 'cupin' superfamily ('cupa' is the Latin term for a small barrel).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 807045907   80 EEHLH-LDDEIRYILDGSGYFDVRDKEdqwirIFMEKGDMVTLPAGIYHRF 129
Cdd:pfam07883  12 PPHRHpGEDEFFYVLEGEGELTVDGEE-----VVLKAGDSVYFPAGVPHRF 57

RmlC-like cupin superfamily; This superfamily contains proteins similar to the RmlC (dTDP (deoxythymidine diphosphates)-4-dehydrorhamnose 3,5-epimerase)-like cupins. RmlC is a dTDP-sugar isomerase involved in the synthesis of L-rhamnose, a saccharide required for the virulence of some pathogenic bacteria. Cupins are a functionally diverse superfamily originally discovered based on the highly conserved motif found in germin and germin-like proteins. This conserved motif forms a beta-barrel fold found in all of the cupins, giving rise to the name cupin ('cupa' is the Latin term for small barrel). The active site of members of this superfamily is generally located at the center of a conserved barrel and usually includes a metal ion. The different functional classes in this superfamily include single domain bacterial isomerases and epimerases involved in the modification of cell wall carbohydrates, two domain bicupins such as the desiccation-tolerant seed storage globulins, and multidomain nuclear transcription factors involved in legume root nodulation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 807045907  81 EHLH-LDDEIRYILDGSGYFDVRDKEdqwiRIFMEKGDMVTLPAGIYHRFTVDEKNYTK 138
Cdd:cd02208   14 PHWHpEQDEIFYVLSGEGELTLDDGE----TVELKAGDIVLIPPGVPHSFVNTSDEPAV 68

AraC-like ligand binding domain; This family represents the arabinose-binding and dimerization domain of the bacterial gene regulatory protein AraC. The domain is found in conjunction with the helix-turn-helix (HTH) DNA-binding motif pfam00165. This domain is distantly related to the Cupin domain pfam00190.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 807045907   79 YEEHLHLDDEIRYILDGSGYFDVRDKedqwiRIFMEKGDMVTLPAGIYHRFTVD-EKNYTKAMRLFVGEPVWTA 151
Cdd:pfam02311  16 FPPHVHDFYVIGYIERGVGRFRLNGR-----TYHLGPGDLFLLPPGEPHDYEPEsEDGWRYRWLYFEPELLERI 84

gentisate 1,2-dioxygenase, 1-hydroxy-2-naphthoate dioxygenase, and salicylate 1,2-dioxygenase, N-terminal cupin domain; This family includes the N-terminal cupin domains of three closely related bicupin aromatic ring-cleaving dioxygenases: gentisate 1,2-dioxygenase (GDO), salicylate 1,2-dioxygenase (SDO), and 1-hydroxy-2-naphthoate dioxygenase (NDO). GDO catalyzes the cleavage of the gentisate (2,5-dihydroxybenzoate) aromatic ring, a key step in the gentisate degradation pathway allowing soil bacteria to utilize 2,5-xylenol, 3,5-xylenol, and m-cresol as sole carbon and energy sources. NDO catalyzes the cleavage of 1-hydroxy-2-naphthoate as part of the bacterial phenanthrene degradation pathway. SDO is a ring cleavage dioxygenase from Pseudaminobacter salicylatoxidans that oxidizes salicylate to 2-oxohepta-3,5-dienedioic acid via a novel ring fission mechanism. SDO differs from other known GDOs and NDOs in its unique ability to oxidatively cleave many different salicylate, gentisate and 1-hydroxy-2-naphthoate substrates with high catalytic efficiency. The active site of these enzymes is located in the N-terminal domain but could be influenced by changes in the C-terminal domain, which lacks the strictly conserved metal-binding residues found in other cupin domains and is thought to be an inactive vestigial remnant.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 807045907  82 HLHLDDEIRYILDGSGYFDVRDKEdqwiRIFMEKGDMVTLPAGIYH 127
Cdd:cd02216   37 HRHTPNALRFVLEGPGAYTTVDGE----RCDMEPGDLILTPPGTWH 78

monomeric dehydratase Pac13 and related proteins, cupin domain; This family includes a small monomeric dehydratase Pac13 that mediates the formation of the 3'-deoxynucleotide of pacidamycins, which are uradyl peptide antibiotics (UPAs). Pac13 is involved in the formation of the unique 3'-deoxyuridine moiety found in these UPAs; it catalyzes the dehydration of uridine-5'-aldehyde. The similarity of the 3'-deoxy pacidamycin moiety with synthetic anti-retrovirals, offers a potential opportunity for the utilization of Pac13 in the biocatalytic generation of antiviral compounds. Proteins in this family belong to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold capable of homodimerization.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 807045907  80 EEHLHLDD-EIRYILDGSGYFDVrdkEDQWIRIfmEKGDMVTLPAGIYHRF 129
Cdd:cd20295   34 EEHYHKKStEIYYVLEGEGIFEL---DGEAVPV--KPGDLVLIPPGTRHRA 79