Pfam PF01829: Peptidase A6 family (domain)
Aspartic peptidases, also known as aspartyl proteases (3.4.23.-), are widely distributed proteolytic enzymes  known to exist in vertebrates, fungi, plants, protozoa, bacteria, archaea, retroviruses and some plant viruses. All known aspartic peptidases are endopeptidases. A water molecule, activated by two aspartic acid residues, acts as the nucleophile in catalysis. Aspartic peptidases can be grouped into five clans, each of which shows a unique structural fold .


 * Peptidases in clan AA are either bilobed (family A1 or the pepsin family) or are a homodimer (all other families in the clan, including retropepsin from HIV-1/AIDS) . Each lobe consists of a single domain with a closed Î²-barrel and each lobe contributes one Asp to form the active site. Most peptidases in the clan are inhibited by the naturally occurring small-molecule inhibitor pepstatin .
 * Clan AC contains the single family A8: the signal peptidase 2 family. Members of the family are found in all bacteria. Signal peptidase 2 processes the premurein precursor, removing the signal peptide. The peptidase has four transmembrane domains and the active site is on the periplasmic side of the cell membrane. Cleavage occurs on the amino side of a cysteine where the thiol group has been substituted by a diacylglyceryl group. Site-directed mutagenesis has identified two essential aspartic acid residues which occur in the motifs GNXXDRX and FNXAD (where X is a hydrophobic residue) . No tertiary structures have been solved for any member of the family, but because of the intramembrane location, the structure is assumed not to be pepsin-like.
 * Clan AD contains two families of transmembrane endopeptidases: A22 and A24. These are also known as "GXGD peptidases" because of a common GXGD motif which includes one of the pair of catalytic aspartic acid residues. Structures are known for members of both families and show a unique, common fold with up to nine transmembrane regions . The active site aspartic acids are located within a large cavity in the membrane into which water can gain access .
 * Clan AE contains two families, A25 and A31. Tertiary structures have been solved for members of both families and show a common fold consisting of an Î±-Î²-Î± sandwich, in which the Î² sheet is five stranded .
 * Clan AF contains the single family A26. Members of the clan are membrane-proteins with a unique fold. Homologues are known only from bacteria. The structure of omptin (also known as OmpT) shows a cylindrical barrel containing ten Î² strands inserted in the membrane with the active site residues on the outer surface .
 * There are two families of aspartic peptidases for which neither structure nor active site residues are known and these are not assigned to clans. Family A5 includes thermopsin, an endopeptidase found only in thermophilic archaea. Family A36 contains sporulation factor SpoIIGA, which is known to process and activate sigma factor E, one of the transcription factors that controls sporulation in bacteria .

This group of proteins, which include the Nodavirus coat precusor endopeptidases, are aspartic peptidases that belong to the MEROPS peptidase family A6 (clan AB).

Nodaviruses are small, icosahedral viruses, pathogenic to insects and mammals. A virus particle consists of a single virion, within which is packaged two RNA stands, RNA1 and RNA2.Nodavirus coat precursor endopeptidase (also known as protein alpha) is the only protein encoded by RNA2. During the process of virion assembly, this precursor is cleaved into coat proteins beta and gamma. RNA1 encodes two proteins, at least one of which is involved in RNA replication. The relatively uncomplicated nature of their structural protein and RNA constituents make the nodaviruses a good virus model .

The 3D structure of the capsid protein has been determined by X-ray crystallography to 2.8A resolution . The structure contains a Î²-barrel domain, with a prominent protrusion composed largely of Î²-sheet. This protrusion, together with similar protrusions from neighbouring subunits, forms a prominent trigonal pyramid with quasi-3-fold symmetry . Two Î±-helices extend toward the interior of the particle .