The name of this superfamily has been modified since the most recent official CATH+ release (v4_2_0). At the point of the last release, this superfamily was: waiting to be named.

Functional Families

Overview of the Structural Clusters (SC) and Functional Families within this CATH Superfamily. Clusters with a representative structure are represented by a filled circle.

Superfamily: Malate/L-lactate/L-sulpholactate dehydrogenase, four-helix barrel

This superfamily consists of an alpha-helical domain found in bacterial and archaeal enzymes with malate, L-lactate, L-sulpholactate dehydrogenase activities. The malate dehydrogenase (MDH) of some extremophilies is more similar to the L-lactate dehydrogenases (L-LDH) from various sources than to other MDHs. The archaebacterial MDH deviates from the eubacterial and eukaryotic enzymes having a low selectivity for the coenzyme (NAD(H) or NADP(H)) and catalysing the reduction of oxaloacetate to malate more efficiently than the reverse reaction. It has been suggested that this class of dinucleotide cofactor-dependent dehydrogenases do not contain a Rossman-fold motif, as it was prior believed to be the case. The domain is also found in a variety of enzymes, such as: bacterial and archaeal NAD(P)-dependent malate and lactate dehydrogenases including MjSLDH from thermophilic methanogen Methanocaldococcus jannaschii, (S)-ureidoglycolate dehydrogenase (AllD), and 2,3-diketo-L-gulonate reductase (YiaK) from E. coli.

The Methanoarchaeal sulpholactate dehydrogenase MjSLDH is a dimer, each polypeptide chain being organised in two domains - the largest domain, a dinucleotide-binding domain that contains both chain termini and most of the active site residues and a mobile domain that covers the active site. This domain is described to have a four-helix barrel topology which form an antiparallel pack, and is different from the typical four-helix bundle.

The Pseudomonas syringae homologous dimeric enzyme is PsDpkA, whose monomer is composed of 3 different domains - domain I, domain II (NADPH binding domain), and domain III. Domain I is the helical domain represented in this superfamily, and is described to have a pseudo four-helix bundle structure. The core of the NADPH binding domain consists of a seven-stranded predominantly antiparallel beta-sheet fold (also known as SESAS), which is specific to the MDH/LDH superfamily. Domains I and III are mobile and change their conformations as rigid bodies to produce the catalytic form upon substrate binding. The conformational change to the catalytic form plays important roles in substrate recognition and the catalytic process. The NADPH binding cavity is formed at the domain interface and at the subunit interface with the nicotinamide-ribose moiety of NADPH directly interacting with one side of the antiparallel beta-sheet of domain II.

Another member of this superfamily is (S)-ureidoglycolate dehydrogenase (AllD), an enzyme involed in nitrogen metabolism which converts (S)-ureidoglycolate, a key intermediate in the purine degradation pathway, to oxalurate in an NAD(P)-dependent manner. It also folds into three distinct domains - domain I, domain II and domain III. Domain I contains N- and C-terminal regions and consists of the four-helix bundle similarly to the other enzymes previously described.

PFAM:PF02615, INTERPRO:IPR036111,PMID:15014443,PMID:16192274,PMID:23284870,PMID:14718529

GO Diversity

Unique GO annotations
11 Unique GO terms

EC Diversity

Unique EC annotations
22 Unique EC terms

Species Diversity

Unique species annotations
4135 Unique species

Sequence/Structure Diversity

Overview of the sequence / structure diversity of this superfamily compared to other superfamilies in CATH. Click on the chart to view the data in more detail.

Superfamily Summary

A general summary of information for this superfamily.
Domains: 58
Domain clusters (>95% seq id): 11
Domain clusters (>35% seq id): 10
Unique PDBs: 18
Structural Clusters (5A): 1
Structural Clusters (9A): 1
FunFam Clusters: 4
Unique EC: 22
Unique GO: 11
Unique Species: 4135