Protein Family Models

The alpha-helical Nlig-Ia domain is found at the N-terminal of DNA ligases and it has been proposed to either swivel the NAD+ close to the ligase active site lysine on the RAGNYA domain or function as an allosteric NAD+ binding site. The Nlig-Ia domain is also observed as a solo protein in phages that do not encode a separate NAD+-dependent ligase catalytic module, suggesting the domain can function independently of a DNA ligase. It has been proposed that these domains likely function as NAD+ sensors which might help indicate to the phage the development of NADase host effectors or shield NAD+ from the action of such effectors [1-3]. [1]. 36146784. Apprehending the NAD(+)-ADPr-Dependent Systems in the Virus World. Iyer LM, Burroughs AM, Anantharaman V, Aravind L;. Viruses. 2022;14:1977. [2]. 22230472. Structure guided understanding of NAD+ recognition in bacterial DNA ligases. Lahiri SD, Gu RF, Gao N, Karantzeni I, Walkup GK, Mills SD;. ACS Chem Biol. 2012;7:571-580. [3]. 11781321. Conserved residues in domain Ia are required for the reaction of Escherichia coli DNA ligase with NAD+. Sriskanda V, Shuman S;. J Biol Chem. 2002;277:9695-9700. (from Pfam)

Date:

2024-10-29

Date:

2024-08-14

The HhH domain of DisA, a bacterial checkpoint control protein, is a DNA-binding domain [2]. [1]. 8692686. The helix-hairpin-helix DNA-binding motif: a structural basis for non-sequence-specific recognition of DNA. Doherty AJ, Serpell LC, Ponting CP;. Nucleic Acids Res 1996;24:2488-2497. [2]. 18439896. Structural biochemistry of a bacterial checkpoint protein reveals diadenylate cyclase activity regulated by DNA recombination intermediates. Witte G, Hartung S, Buttner K, Hopfner KP;. Mol Cell. 2008;30:167-178. (from Pfam)

Date:

2024-10-16

DNA ligases catalyse the crucial step of joining the breaks in duplex DNA during DNA replication, repair and recombination, utilising either ATP or NAD(+) as a cofactor [1]. This family is a small zinc binding motif that is presumably DNA binding [1]. IT is found only in NAD dependent DNA ligases [1]. [1]. 10698952. Crystal structure of NAD(+)-dependent DNA ligase: modular architecture and functional implications. Lee JY, Chang C, Song HK, Moon J, Yang JK, Kim HK, Kwon ST, Suh SW;. EMBO J 2000;19:1119-1129. (from Pfam)

Date:

2024-10-16

DNA ligases catalyse the crucial step of joining the breaks in duplex DNA during DNA replication, repair and recombination, utilising either ATP or NAD(+) as a cofactor [1]. This family is a small domain found after the adenylation domain Pfam:PF01653 in NAD dependent ligases [1]. OB-fold domains generally are involved in nucleic acid binding. [1]. 10698952. Crystal structure of NAD(+)-dependent DNA ligase: modular architecture and functional implications. Lee JY, Chang C, Song HK, Moon J, Yang JK, Kim HK, Kwon ST, Suh SW;. EMBO J 2000;19:1119-1129. (from Pfam)

Date:

2024-10-16

DNA ligases catalyse the crucial step of joining the breaks in duplex DNA during DNA replication, repair and recombination, utilising either ATP or NAD(+) as a cofactor [1]. This domain is the catalytic adenylation domain. The NAD+ group is covalently attached to this domain at the lysine in the KXDG motif of this domain. This enzyme- adenylate intermediate is an important feature of the proposed catalytic mechanism [1]. [1]. 10698952. Crystal structure of NAD(+)-dependent DNA ligase: modular architecture and functional implications. Lee JY, Chang C, Song HK, Moon J, Yang JK, Kim HK, Kwon ST, Suh SW;. EMBO J 2000;19:1119-1129. [2]. 11368162. Mutational analyses of Aquifex pyrophilus DNA ligase define essential domains for self-adenylation and DNA binding activity. Lim JH, Choi J, Kim W, Ahn BY, Han YS;. Arch Biochem Biophys 2001;388:253-260. [3]. 10368271. Structure of the adenylation domain of an NAD+-dependent DNA ligase. Singleton MR, Hakansson K, Timson DJ, Wigley DB;. Structure Fold Des 1999;7:35-42. (from Pfam)

Date:

2024-10-16

The BRCT domain is found predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage. The BRCT domain of XRCC1 forms a homodimer in the crystal structure. This suggests that pairs of BRCT domains associate as homo- or heterodimers. BRCT domains are often found as tandem-repeat pairs [2]. Structures of the BRCA1 BRCT domains revealed a basis for a widely utilised head-to-tail BRCT-BRCT oligomerisation mode [3]. This conserved tandem BRCT architecture facilitates formation of the canonical BRCT phospho-peptide interaction cleft at a groove between the BRCT domains. Disease associated missense and nonsense mutations in the BRCA1 BRCT domains disrupt peptide binding by directly occluding this peptide binding groove, or by disrupting key conserved BRCT core folding determinants [5]. Original discovery of duplicated domain in BRCA1. [1]. 8673121. BRCA1 protein products ...Functional motifs... Koonin EV, Altschul SF, Bork P;. Nature Genet 1996;13:266-268. Extension of BRCT superfamily. [2]. 15501676. Interactions between BRCT repeats and phosphoproteins: tangled up in two. Glover JN, Williams RS, Lee MS;. Trends Biochem Sci. 2004;29:579-585. [3]. 11573086. Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1. Williams RS, Green R, Glover JN;. Nat Struct Biol. 2001;8:838-842. [4]. 15133503. Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1. Williams RS, Lee MS, Hau DD, Glover JN;. Nat Struct Mol Biol. 2004;11:519-525. [5]. 14534301. Detection of protein folding defects caused by BRCA1-BRCT truncation and missense mutations. Williams. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-10-16