InterPro domain: IPR020568

Domain 2 of the ribosomal protein S5 has a left-handed, 2-layer alpha/beta fold with a core structure consisting of beta(3)-alpha-beta-alpha. Domains with this fold are found in numerous RNA/DNA-binding proteins, as well as in kinases from the GHMP kinase family. Proteins containing this alpha/beta fold domain include:

• Translational machinery components (ribosomal proteins S5 and S9, and domain IV of elongation factors EF-G and eEF-2) [ 1 ].
• Ribonuclease P protein (RNase P) [ 2 ].
• Ribonuclease PH (domain 1) [ 3 ], as well as various exosome complex exonucleases (RRP41, RRP42, RRP43, RRP45, RRP46, MTR3, ECX1, ECX2) [ 4 ].
• DNA modification proteins (DNA mismatch repair proteins MutL and PMS2, DNA gyrase B, DNA topoisomerase II, IV-B and VI-B) [ 5 ].
• GHMP kinases that transfer a phosphoryl group from ATP to an acceptor (galactokinase ( 2.7.1.6 ), homoserine kinase ( 2.7.1.39 ), and mevalonate kinase ( 2.7.1.36 )) [ 6 , 7 ].
• Caenorhabditis elegans early switch protein Xol-1 (a divergent member of the GHMP kinase family that has lost the ATP-binding site) [ 8 ].
• Hsp90 chaperone (middle domain), which is related to the DNA gyrase/MutL family [ 9 ]; this domain contains an extra C-terminal alpha/beta subdomain.
• Imidazole glycerol phosphate dehydratase, which contains a duplication consisting of two structural repeats of this fold [ 10 ].
• The catalytic domain of ATP-dependent protease Lon (La), which contains an extra C-terminal alpha/beta subdomain [ 11 ].
• Formaldehyde-activating enzyme FAE, which contains a modification of this fold consisting of an extra alpha/beta unit after strand 2 [ 12 ].

1. Structures of prokaryotic ribosomal proteins: implications for RNA binding and evolution. Biochem. Cell Biol. 73, 979-86
2. Structure and function of eukaryotic Ribonuclease P RNA. Mol. Cell 24, 445-56
3. Crystal structure of the phosphorolytic exoribonuclease RNase PH from Bacillus subtilis and implications for its quaternary structure and tRNA binding. Protein Sci. 13, 668-77
4. Reconstitution, activities, and structure of the eukaryotic RNA exosome. Cell 127, 1223-37
5. Structure and function of the N-terminal 40 kDa fragment of human PMS2: a monomeric GHL ATPase. EMBO J. 20, 5521-31
6. Molecular functions of conserved aspects of the GHMP kinase family. Biochemistry 43, 14594-601
7. Structure and mechanism of homoserine kinase: prototype for the GHMP kinase superfamily. Structure 8, 1247-57
8. XOL-1, primary determinant of sexual fate in C. elegans, is a GHMP kinase family member and a structural prototype for a class of developmental regulators. Genes Dev. 17, 977-90
9. Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery. EMBO J. 23, 1402-10
10. Crystal structure of imidazole glycerol-phosphate dehydratase: duplication of an unusual fold. J. Biol. Chem. 279, 15491-8
11. The catalytic domain of Escherichia coli Lon protease has a unique fold and a Ser-Lys dyad in the active site. J. Biol. Chem. 279, 8140-8
12. How an enzyme binds the C1 carrier tetrahydromethanopterin. Structure of the tetrahydromethanopterin-dependent formaldehyde-activating enzyme (Fae) from Methylobacterium extorquens AM1. J. Biol. Chem. 280, 13712-9