Inhibition of the key procoagulant enzyme, thrombin, by canonically binding Kunitz-type inhibitors is unfavourable due to the presence of a prominent insertion loop at position 60, and of a glutamate at position 192.
These structures are formed by large insertion loops within the MCP of gokushoviruses and are absent in the microviral MCPs [45].
Tcas_pHCl also has an insertion in loop C (Variant 4, Fig. 8C) which is likely to impact on ligand binding.
Very recently, the syndecan-binding protein synbindin, involved in neuronal membrane trafficking, has been found to show a "special" LD-like fold, structurally related to SEDL and split by a loop insertion corresponding to an atypical PDZ domain [ 31].
In StPurL, this cavity entrance is blocked by a loop insertion of residues 668−677, which interacts with helix α24 (α17 of TmPurL), and further blocked off by the glutaminase domain, making the nucleotide structural in StPurL and likely inserted during protein folding.
The phosphotransfer site H147RD (L/V/isxxRNxL156 is also present in the catalytic loop of all VKRs but in the insect VKRs of P. humanus corporis and H. saltator, this motif is interrupted by an insertion.
In human Rev1, the finger and thumb are connected by a long loop insertion, and the CC is ring-shaped and encircles the DNA substrate.
A central domain, the domain I, is formed by eight β-strand barrels containing two insertion loops.
Slow dissociation from actin is attributed to tethering by a unique Loop 2 insertion.
This loop is modulated by an inhibitory side loop represented by molecular layer interneurons (MLIs, blue).
