Crystal structure of shrimp arginine kinase in binary complex with arginine—a molecular view of the phosphagen precursor binding to the enzyme

Abstract

Arginine kinase (AK) is a key enzyme for energetic balance in invertebrates. Although AK is a well-studied system that provides fast energy to invertebrates using the phosphagen phospho-arginine, the structural details on the AK-arginine binary complex interaction remain unclear. Herein, we determined two crystal structures of the Pacific whiteleg shrimp (Litopenaeus vannamei) arginine kinase, one in binary complex with arginine (LvAK-Arg) and a ternary transition state analog complex (TSAC). We found that the arginine guanidinium group makes ionic contacts with Glu225, Cys271 and a network of ordered water molecules. On the zwitterionic side of the amino acid, the backbone amide nitrogens of Gly64 and Val65 coordinate the arginine carboxylate. Glu314, one of proposed acid-base catalytic residues, did not interact with arginine in the binary complex. This residue is located in the flexible loop 310-320 that covers the active site and only stabilizes in the LvAK-TSAC. This is the first binary complex crystal structure of a guanidine kinase in complex with the guanidine substrate and could give insights into the nature of the early steps of phosphagen biosynthesis.

The Substrate-free and -bound Crystal Structures of the Duplicated Taurocyamine Kinase from the Human Parasite Schistosoma mansoni

“…2). Hence, in line with what has been described for CK and AK (25,33,34), binding of the guanidino substrate is not the main determinant of the conformational change cascade observed for the TSA complex.…”

“…According to a search for structural homologs performed with DALI (65), these lobes are most similar to substrate-free AKs. The highest similarity score (Z ϭ 46) was obtained between lobe D1 and the monomeric AK of Litopenaeus vannamei (LvAK) (25), with 47% sequence identity and a root mean square deviation of 1.5 Å for 339 C␣ pairs.…”

Structure of a double-domain phosphagen kinase reveals an asymmetric arrangement of the tandem domains

“…values among the four ddAK structures (0.2-0.6 Å for D1 and 0.3-0.4 Å for D2). Actually, somewhat similar situations have been observed in previous crystallographic studies of single-domain PKs (Wu et al, 2010;Bush et al, 2011;Ló pez-Zavala et al, 2013), indicating that a TSAC of PK is needed to reach the fully closed state, which we failed to approach. For the ddAKarginine-ATPS complex crystals obtained by soaking, the packing forces could be the restraints that prevent further allostery that might assist ligand binding to the other domain.…”

Biochemical and structural characterization of a novel arginine kinase from the spiderPolybetes pythagoricus

“…347 amino acid residues were fitted in the final model (see Tables 2 and 3 for statistical details), as in apo- Pp AK structure residues 310–320 are disordered. Arg- Pp AK binary complex was found is the open conformation similar to the free substrate Pp AK model ( Lopez-Zavala et al, 2013 ). Superposition of both structures do not show overall conformational changes upon arginine binding (RMSD = 0.36 Å for C-α atoms) ( Fig.…”

“…Structural characterization has been focused in both free-ligand and fully occupied active site of AK, that are called open and closed conformation, respectively ( Fernandez et al, 2007 ; Pruett et al, 2003 ; Zhou et al, 1998 ). Only, a few reports show structural details of binding of arginine in a binary complex, which is a crucial step during catalysis ( Lopez-Zavala et al, 2013 ; Wang et al, 2015 ). To date, horseshoe crab crystal structure has been reported for Chelicerate, which is comprised of more than 75,000 species ( Strong & Ellington, 1995 ).…”