PDBsum entry 1e22

Ligase

PDB id

1e22

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Contents

			Protein chain

					485 a.a. *

			Ligands

					LYS


					ACP


					GOL ×6

			Metals

					_MG ×3

			Waters ×306

* Residue conservation analysis

PDB id:

1e22

Links

Name:

Ligase

Title:

Lysyl-tRNA synthetase (lysu) hexagonal form complexed with lysine and the non-hydrolysable atp analogue amp-pcp

Structure:

Lysyl-tRNA synthetase. Chain: a. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 83333. Strain: k-12. Cellular_location: cytoplasm. Gene: lysu. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Homo-Dimer (from PDB file)

Resolution:

2.43Å

R-factor:

0.176

R-free:

0.228

Authors:

G.Desogus,F.Todone,P.Brick,S.Onesti

Key ref:

G.Desogus et al. (2000). Active site of lysyl-tRNA synthetase: structural studies of the adenylation reaction. Biochemistry, 39, 8418-8425. PubMed id: 10913247 DOI: 10.1021/bi0006722

Date:

15-May-00

Release date:

28-Jul-00

PROCHECK

	Headers

	References

Protein chain

P0A8N5 (SYK2_ECOLI) - Lysine--tRNA ligase, heat inducible from Escherichia coli (strain K12)

Seq: Struc:					505 a.a. 485 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.6.1.1.6 - lysine--tRNA ligase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

tRNA(Lys) + L-lysine + ATP = L-lysyl-tRNA(Lys) + AMP + diphosphate

tRNA(Lys)

L-lysine
Bound ligand (Het Group name = LYS)
corresponds exactly

ATP

L-lysyl-tRNA(Lys)
Bound ligand (Het Group name = ACP)
matches with 74.19% similarity

AMP

diphosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/bi0006722	Biochemistry 39:8418-8425 (2000)
PubMed id: 10913247

Active site of lysyl-tRNA synthetase: structural studies of the adenylation reaction.
G.Desogus, F.Todone, P.Brick, S.Onesti.

ABSTRACT

Aminoacyl-tRNA synthetases play a key role in protein biosynthesis by catalyzing the specific aminoacylation of tRNA. The energy required for the formation of the ester bond between the amino acid carboxylate group and the tRNA acceptor stem is supplied by coupling the reaction to the hydrolysis of ATP. Lysyl-tRNA synthetase from Escherichia coli belongs to the family of class II synthetases and carries out a two-step reaction, in which lysine is activated by being attached to the alpha-phosphate of AMP before being transferred to the cognate tRNA. Crystals of the thermo-inducible E. coli lysyl-tRNA synthetase LysU which diffract to 2.1 A resolution have been used to determine crystal structures of the enzyme in the presence of lysine, the lysyl-adenylate intermediate, and the nonhydrolyzable ATP analogue AMP-PCP. Additional data have been obtained from crystals soaked in a solution containing ATP and Mn(2+). The refined crystal structures give "snapshots" of the active site corresponding to key steps in the aminoacylation reaction and provide the structural framework for understanding the mechanism of lysine activation. The active site of LysU is shaped to position the substrates for the nucleophilic attack of the lysine carboxylate on the ATP alpha-phosphate. No residues are directly involved in catalysis, but a number of highly conserved amino acids and three metal ions coordinate the substrates and stabilize the pentavalent transition state. A loop close to the catalytic pocket, disordered in the lysine-bound structure, becomes ordered upon adenine binding.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21213248

D.V.Palanivelu, A.Goepfert, M.Meury, P.Guye, C.Dehio, and T.Schirmer (2011).
Fic domain-catalyzed adenylylation: insight provided by the structural analysis of the type IV secretion system effector BepA.

Protein Sci, 20, 492-499.

PDB codes:

2jk8 2vy3 2vza

20729861

T.Yanagisawa, T.Sumida, R.Ishii, C.Takemoto, and S.Yokoyama (2010).
A paralog of lysyl-tRNA synthetase aminoacylates a conserved lysine residue in translation elongation factor P.

Nat Struct Mol Biol, 17, 1136-1143.

PDB codes:

3a5y 3a5z

20670890

W.W.Navarre, S.B.Zou, H.Roy, J.L.Xie, A.Savchenko, A.Singer, E.Edvokimova, L.R.Prost, R.Kumar, M.Ibba, and F.C.Fang (2010).
PoxA, yjeK, and elongation factor P coordinately modulate virulence and drug resistance in Salmonella enterica.

Mol Cell, 39, 209-221.

PDB code:

3g1z

19505149

F.Fan, and J.S.Blanchard (2009).
Toward the catalytic mechanism of a cysteine ligase (MshC) from Mycobacterium smegmatis: an enzyme involved in the biosynthetic pathway of mycothiol.

Biochemistry, 48, 7150-7159.

19174549

H.Sakurama, T.Takita, B.Mikami, T.Itoh, K.Yasukawa, and K.Inouye (2009).
Two crystal structures of lysyl-tRNA synthetase from Bacillus stearothermophilus in complex with lysyladenylate-like compounds: insights into the irreversible formation of the enzyme-bound adenylate of L-lysine hydroxamate.

J Biochem, 145, 555-563.

PDB codes:

3e9h 3e9i

18076053

D.Thompson, C.Lazennec, P.Plateau, and T.Simonson (2008).
Probing electrostatic interactions and ligand binding in aspartyl-tRNA synthetase through site-directed mutagenesis and computer simulations.

Proteins, 71, 1450-1460.

18180246

N.Shen, M.Zhou, B.Yang, Y.Yu, X.Dong, and J.Ding (2008).
Catalytic mechanism of the tryptophan activation reaction revealed by crystal structures of human tryptophanyl-tRNA synthetase in different enzymatic states.

Nucleic Acids Res, 36, 1288-1299.

PDB codes:

2quh 2qui 2quj 2quk

19022179

T.Yanagisawa, R.Ishii, R.Fukunaga, T.Kobayashi, K.Sakamoto, and S.Yokoyama (2008).
Multistep engineering of pyrrolysyl-tRNA synthetase to genetically encode N(epsilon)-(o-azidobenzyloxycarbonyl) lysine for site-specific protein modification.

Chem Biol, 15, 1187-1197.

PDB codes:

2zin 2zio

17690095

D.Thompson, C.Lazennec, P.Plateau, and T.Simonson (2007).
Ammonium scanning in an enzyme active site. The chiral specificity of aspartyl-tRNA synthetase.

J Biol Chem, 282, 30856-30868.

17592110

J.M.Kavran, S.Gundllapalli, P.O'Donoghue, M.Englert, D.Söll, and T.A.Steitz (2007).
Structure of pyrrolysyl-tRNA synthetase, an archaeal enzyme for genetic code innovation.

Proc Natl Acad Sci U S A, 104, 11268-11273.

PDB codes:

2q7e 2q7g 2q7h 2zim

18073113

M.Kuratani, Y.Yoshikawa, Y.Bessho, K.Higashijima, T.Ishii, R.Shibata, S.Takahashi, K.Yutani, and S.Yokoyama (2007).
Structural basis of the initial binding of tRNA(Ile) lysidine synthetase TilS with ATP and L-lysine.

Structure, 15, 1642-1653.

PDB codes:

2e21 2e89

17428498

P.Retailleau, V.Weinreb, M.Hu, and C.W.Carter (2007).
Crystal structure of tryptophanyl-tRNA synthetase complexed with adenosine-5' tetraphosphate: evidence for distributed use of catalytic binding energy in amino acid activation by class I aminoacyl-tRNA synthetases.

J Mol Biol, 369, 108-128.

PDB code:

2ov4

17158446

T.F.Chou, and C.R.Wagner (2007).
Lysyl-tRNA synthetase-generated lysyl-adenylate is a substrate for histidine triad nucleotide binding proteins.

J Biol Chem, 282, 4719-4727.

16408313

D.Thompson, P.Plateau, and T.Simonson (2006).
Free-energy simulations and experiments reveal long-range electrostatic interactions and substrate-assisted specificity in an aminoacyl-tRNA synthetase.

Chembiochem, 7, 337-344.

16774919

D.Thompson, and T.Simonson (2006).
Molecular dynamics simulations show that bound Mg2+ contributes to amino acid and aminoacyl adenylate binding specificity in aspartyl-tRNA synthetase through long range electrostatic interactions.

J Biol Chem, 281, 23792-23803.

16317719

S.J.Hughes, J.A.Tanner, A.D.Miller, and I.R.Gould (2006).
Molecular dynamics simulations of LysRS: an asymmetric state.

Proteins, 62, 649-662.

16595681

Z.Tokgöz, R.N.Bohnsack, and A.L.Haas (2006).
Pleiotropic effects of ATP.Mg2+ binding in the catalytic cycle of ubiquitin-activating enzyme.

J Biol Chem, 281, 14729-14737.

15657145

M.A.Swairjo, and P.R.Schimmel (2005).
Breaking sieve for steric exclusion of a noncognate amino acid from active site of a tRNA synthetase.

Proc Natl Acad Sci U S A, 102, 988-993.

PDB codes:

1yfr 1yfs 1yft 1ygb

12660169

C.Charron, H.Roy, M.Blaise, R.Giegé, and D.Kern (2003).
Non-discriminating and discriminating aspartyl-tRNA synthetases differ in the anticodon-binding domain.

EMBO J, 22, 1632-1643.

PDB code:

1n9w

14690420

M.L.Bovee, M.A.Pierce, and C.S.Francklyn (2003).
Induced fit and kinetic mechanism of adenylation catalyzed by Escherichia coli threonyl-tRNA synthetase.

Biochemistry, 42, 15102-15113.

12787471

S.J.Hughes, J.A.Tanner, A.D.Hindley, A.D.Miller, and I.R.Gould (2003).
Functional asymmetry in the lysyl-tRNA synthetase explored by molecular dynamics, free energy calculations and experiment.

BMC Struct Biol, 3, 5.

11809762

C.T.Lemke, and P.L.Howell (2002).
Substrate induced conformational changes in argininosuccinate synthetase.

J Biol Chem, 277, 13074-13081.

PDB codes:

1kp2 1kp3

12029131

G.Srinivasan, C.M.James, and J.A.Krzycki (2002).
Pyrrolysine encoded by UAG in Archaea: charging of a UAG-decoding specialized tRNA.

Science, 296, 1459-1462.

11604396

J.A.Tanner, A.Abowath, and A.D.Miller (2002).
Isothermal titration calorimetry reveals a zinc ion as an atomic switch in the diadenosine polyphosphates.

J Biol Chem, 277, 3073-3078.

12221282

J.J.May, N.Kessler, M.A.Marahiel, and M.T.Stubbs (2002).
Crystal structure of DhbE, an archetype for aryl acid activating domains of modular nonribosomal peptide synthetases.

Proc Natl Acad Sci U S A, 99, 12120-12125.

PDB codes:

1md9 1mdb 1mdf

12019264

T.Takita, and K.Inouye (2002).
Transition state stabilization by the N-terminal anticodon-binding domain of lysyl-tRNA synthetase.

J Biol Chem, 277, 29275-29282.

11679717

R.Fishman, V.Ankilova, N.Moor, and M.Safro (2001).
Structure at 2.6 A resolution of phenylalanyl-tRNA synthetase complexed with phenylalanyl-adenylate in the presence of manganese.

Acta Crystallogr D Biol Crystallogr, 57, 1534-1544.

PDB code:

1jjc

11041850

S.Onesti, G.Desogus, A.Brevet, J.Chen, P.Plateau, S.Blanquet, and P.Brick (2000).
Structural studies of lysyl-tRNA synthetase: conformational changes induced by substrate binding.

Biochemistry, 39, 12853-12861.

PDB codes:

1bbu 1bbw

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.