Protein Data Bank

Htr A

Telomerase is a unique ribonucleoprotein complex that catalyzes the addition of telomeric DNA repeats onto the 3' ends of linear chromosomes. All vertebrate telomerase RNAs contain a catalytically essential core domain that includes the template and a pseudoknot with extended helical subdomains. Within these helical regions is an asymmetric 5-nt internal bulge loop (J2a/b) flanked by helices (P2a and P2b) that is highly conserved in its location but not sequence. NMR structure determination reveals that J2a/b forms a defined S-shape and creates an ?90 ° bend with a surprisingly low twist (?10 °) between the flanking helices. A search of RNA structures revealed only one other example of a 5-nt bulge, from hepatitis C virus internal ribosome entry site, with a different sequence but the same structure. J2a/b is intrinsically flexible but the interhelical motions across the loop are remarkably restricted. Nucleotide substitutions in J2a/b that affect the bend angle, direction, and interhelical dynamics are correlated with telomerase activity. Based on the structures of P2ab (J2a/b and flanking helices), the conserved region of the pseudoknot (P2b/P3, previously determined) and the remaining helical segment (P2a.1-J2a.1 refined using residual dipolar couplings and the modeling program MC-Sym) we have calculated an NMR-based model of the full-length pseudoknot. The model and dynamics analysis show that J2a/b serves as a dominant structural and dynamical element in defining the overall topology of the core domain, and suggest that interhelical motions in P2ab facilitate nucleotide addition along the template and template translocation.

Molecule:	35-MER
Polymer:	1	Type:	polyribonucleotide	Length:	35
Chains:	A

Source

Polymer: 1

Scientific   Name:

Synthetic construct

LonA

The structure of a recombinant construct consisting of residues 1-245 of Escherichia coli Lon protease, the prototypical member of the A-type Lon family, is reported. This construct encompasses all or most of the N-terminal domain of the enzyme. The structure was solved by SeMet SAD to 2.6 A resolution utilizing trigonal crystals that contained one molecule in the asymmetric unit. The molecule consists of two compact subdomains and a very long C-terminal alpha-helix. The structure of the first subdomain (residues 1-117), which consists mostly of beta-strands, is similar to that of the shorter fragment previously expressed and crystallized, whereas the second subdomain is almost entirely helical. The fold and spatial relationship of the two subdomains, with the exception of the C-terminal helix, closely resemble the structure of BPP1347, a 203-amino-acid protein of unknown function from Bordetella parapertussis, and more distantly several other proteins. It was not possible to refine the structure to satisfactory convergence; however, since almost all of the Se atoms could be located on the basis of their anomalous scattering the correctness of the overall structure is not in question. The structure reported here was also compared with the structures of the putative substrate-binding domains of several proteins, showing topological similarities that should help in defining the binding sites used by Lon substrates.

• Classification:	Hydrolase
  Structure Weight:	29575.20

  Molecule:	ATP-dependent protease La
  Polymer:	1	Type:	polypeptide(L)	Length:	252
  Chains:	A
  EC#:	3.4.21.53
  Fragment:	Lon N-domain (UNP residues 1-245)

   

• Source

  Polymer: 1
  Scientific Name:	Escherichia coli	Taxonomy	Expression System:	Escherichia coli

   

• Related PDB Entries

  Id	Details
  2ANE

   

• Modified Residues

  Identifier		Formula	Parent	Type
  MSE Search		C5 H11 N O2 Se	MET	lPeptideLinking

ClpP

In ClpXP and ClpAP complexes, ClpA and ClpX use the energy of ATP hydrolysis to unfold proteins and translocate them into the self-compartmentalized ClpP protease. ClpP requires the ATPases to degrade folded or unfolded substrates, but binding of acyldepsipeptide antibiotics (ADEPs) to ClpP bypasses this requirement with unfolded proteins. We present the crystal structure of Escherichia coli ClpP bound to ADEP1 and report the structural changes underlying ClpP activation. ADEP1 binds in the hydrophobic groove that serves as the primary docking site for ClpP ATPases. Binding of ADEP1 locks the N-terminal loops of ClpP in a ?-hairpin conformation, generating a stable pore through which extended polypeptides can be threaded. This structure serves as a model for ClpP in the holoenzyme ClpAP and ClpXP complexes and provides critical information to further develop this class of antibiotics.

Classification:	Hydrolase/antibiotic
Structure Weight:	677090.25

Molecule:	ATP-dependent Clp protease proteolytic subunit
Polymer:	1	Type:	polypeptide(L)	Length:	207
Chains:	A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, W, X, Y, Z, a, b
EC#:	3.4.21.92
Molecule:	ACYLDEPSIPEPTIDE 1
Polymer:	2	Type:	polypeptide(L)	Length:	7
Chains:	1, 2, 3, 4, c, d, e, f, g, h, i, j, k, l, m, n, o, p, q, r, s, t, u, v, w, x, y, z

 

Source

Polymer: 1
Scientific Name:	Escherichia coli	Taxonomy	Expression System:	Escherichia coli
Polymer: 2
Scientific Name:	Streptomyces hawaiiensis	Taxonomy