The name of this superfamily has been modified since the most recent official CATH+ release (v4_3_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: ANL, C-terminal domain

This superfamily comprises structural domains found at the N-terminus of various ligases from the ANL superfamily. The name ANL derives from from three of the subfamilies - Acyl-CoA synthetases, the adenylation domains of the modular non-ribosomal peptide synthetases (NRPSs), and the luciferase enzymes. Members of this superfamily include luciferase, long chain fatty acid Co-A ligase, acetyl-CoA synthetase and various other closely-related synthetases as well as a plant auxin-responsive promoter family. These enzymes are involved in catalysing the initial adenylation of a carboxylate to form an acyl-AMP intermediate, followed by a second partial reaction, most commonly the formation of a thioester. These adenylating enzymes utilise a 140 degrees rotation of the C-terminal domain to adopt two distinct conformations that are used for the adenylation and thiolation reactions.

Luciferases are composed of a large N-terminal domain and a smaller C-terminal domain, which form a cleft. The active site of these enzymes is located at the interface between these two domains, with most active site residues located in the N-terminal domain, and two lysine residues in the C-terminal domain. The N-terminal domain is involved in catalysis, and the C-terminal domain is essential for luciferase activation during the catalytic reaction.

The overall structure of the N-terminal domain has been characterised in a fatty acyl-CoA ligase in M. tuberculosis, FA[PfamClan:CL13] and fatty acyl-AMP ligase FAAL28. The N-terminal domain of FA[PfamClan:CL13] consists of three subdomains: subdomains A and B form alpha + beta topology, which pack together to form a five-layered alpha-beta-alpha-beta-alpha tertiary structure. The third subdomain C folds into a distorted beta-barrel topology. In FAAL28, the C-subdomain presents an insertion between beta-strands 1 and 2. A hydrophobic interaction was identified at the interface of insertion and N-terminal domain, and it was suggested to play a fundamental role in anchoring the insertion motif and arresting the acyl-CoA catalysis. The C-terminal domain can adopt two different conformations which allow the catalysis to occur in two steps. After the adenylation step in 'adenylation conformation', the C-terminal domain undergoes a domain alternation of 140 degrees to adopt a 'thiolation conformation' required for the second step of catalysis.

The Mycobacterium tuberculosis fatty acyl-CoA synthetase (ACS) FadD13 is a peripheral membrane protein essential for virulence and intracellular growth of the pathogen. FadD13 was identified to play a central role in lipid metabolism, and therefore would be a possible drug target. FadD13 comprises an N- and a C-terminal domain. The N-terminal domain folds into an alpha+beta topology and can be further divided into two subdomains. The CoA binding site in ACS proteins is formed in the junction between the domains upon a 140 degrees rotation of the C-terminal domain after the initial adenylation step.

Pfam [PfamClan:CL0531], PFAM:PF13193, INTERPRO:IPR042099,PMID:24103420,PMID:22852753,PMID:22206988,PMID:22560731,PMID:22365602

GO Diversity

Unique GO annotations
338 Unique GO terms

EC Diversity

Unique EC annotations
41 Unique EC terms

Species Diversity

Unique species annotations
19627 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: 256
Domain clusters (>95% seq id): 56
Domain clusters (>35% seq id): 30
Unique PDBs: 141
Structural Clusters (5A): 4
Structural Clusters (9A): 2
FunFam Clusters: 170
Unique EC: 41
Unique GO: 338
Unique Species: 19627