Skip to main content

Table 4 Functional information for sites within or neighboring positive selection clusters

From: Structural and functional implications of positive selection at the primate angiogenin gene

Site

Functional information

Selection

Ser4

None

++

Arg5

•Conserved site, unique to ANG (RNase counterpart is Ala4), has been implicated in the formation of hydrogen bonds with the P2 phosphate and appears to be the critical residue in this subsite [42] [45] [76].

•Involved in the contacts of the complex ANG-Ribonuclease Inhibitor (RI) [77].

 

Thr7

None

+

His8

•Structural counterpart of the RNase A P2 subsite residue Lys7 lays 4.5Å apart from the P2 phosphate group in superimposed structures, too far to interact with it. Forms H-bonds with Arg33 [42].

•Involved in the contacts of the complex ANG-RI [77].

+

Phe9

•Part of the hydrophobic nucleus. Forms π-π interactions with catalytic residue His13 [78].

 

Leu10

•Mutation to proline disrupts ribonucleolytic activity (disrupts interaction 9–13) [78].

 

Thr11

•Structural counterpart of the RNase A P2 subsite residue Arg10, but lays too far from the P2 phosphate group in superimposed structures to form interactions [42].

+

Gln12

•Structural analogue of the RNase A P1 subsite residue Gln11 [42].

•Mutation to proline disrupts ribonucleolytic activity (disrupts interaction 9–13) [78].

•Mutation to Leu found in two ALS patients of Scottish/Irish descent [13].

 

His13

•Member of the catalytic triad – general base catalysis [42].

 

Arg31

Region 31–35 constitutes a nuclear location signal responsible for the nucleolar location of angiogenin [20].

•Mutation to alanine significantly reduces nuclear translocation efficiency.

•Involved in the contacts of the complex ANG-RI [77].

•Mutation to Leu found in one ALS patients of Irish/English descent [13].

 

Arg32

 

•Involved in the contacts of the complex ANG-RI [77].

+

Arg33

 

•Mutation to alanine disrupts nuclear translocation [20] and reduces ribonucleolytic activity by 7 fold [45].

•Interacts with Phe45 and shields Met30 and Cys26 from solvent [78].

•H bonds with Thr11 and Tyr14 and Ser28 [42].

 

Gly34

  

++

Leu35

   

Lys40

•Member of the catalytic triad – donates H bond to the pentavalent transition state. Conservative replacement with arginine causes a 50 fold reduction in activity [79].

•Involved in the contacts of the complex ANG-RI [77].

•Mutation to Ile found in three ALS patients of Irish/Scottish descent [13].

 

Asp41

•Involved in the contacts of the complex ANG-RI [77].

++

Ile42

•Structural counterpart of the RNase A B1 subsite residue Val43 [42].

 

Asn43

•Structural counterpart of the RNase A B1 subsite residue Asn44 [42].

 

Arg51

•Flexible residue [42].

•Appears disordered in the ANG–RI complex x-ray structure [77].

+

Ser52

•Forms H-bonds with Asn61 [42].

+

Ile53

•Part of the hydrophobic core, essential to the ribonucleolytic activity [78].

 

Asn61

The region from Lys-60 to Asn-68 constitutes a critical cell-binding site, distinct from the catalytic site [18].

•Deamination abolishes angiogenic activity [19].

•Conserved throughout angiogenins, considered essential for actin binding [48].

•Forms H-bonds with Ser 52 and 74 [42].

 

Gly62

 

•Conserved throughout angiogenins, considered essential for actin binding [48].

 

Asn63

 

•Forms H-bonds with Gly62 [42].

++

Pro64

   

His65

   

Arg66

  

++

Glu67

 

•Involved in the contacts of the complex ANG-RI [77].

 

Thr80

•Structural counterpart of the RNase A B1 subsite residue Asp83 [42].

  

Lys82

None

 

+

His84

•The region 84–89 is involved in the contacts of the complex ANG-RI [77].

++

Cys92

•Forms an S-S bond with Cys39 [42].

 

Gln93

•Involved in the contacts of the complex ANG-RI [77].

+

Tyr94

•Forms H-bonds with Lys-40 and is part of the hydrophobic core, mutation to asparagine abolishes ribonucleolytic activity [78].

 

Val103

•Part of the hydrophobic core, mutation to Asp abolishes ribonucleolytic activity [78].

+

  1. Sites under positive selection are indicated in the last column, (++) type I sites, (+) type II sites.