PROTEIN DATA BANK

         Protein Data Bank is a repository for 3-D biological macromolecular structure.All data are available to the public.It includes proteins, nucleic acids and viruses.Obtained by X-Ray crystallography (80%) or NMR spectroscopy (16%).Submitted by biologists and biochemists from around the world.Founded in 1971 by Brookhaven National Laboratory, New York.First set of data were entered on punched cards.  Then with magnetic tapes.Transferred to the Research Collaborators for Structural Bioinformatics (RCSB) in 1998.Currently it holds 29,000 released structures.PDB is an important resource for research in the academic,pharmaceutical,and biotechnology sectors,

                                                   FTSH PEPTIDASE

Crystal structure of PBP3 complexed with MC-1 Authors: Han, S.,   Evdokimov, A. Release Date: 2010-12-22 Classification: Hydrolase/antibiotic    Experiment: X-RAY DIFFRACTION with resolution of 1.64 Å Compound: 1 Polymer 1 Ligand   Image Identifier Name Formula MC8   2-({[(1Z)-1-(2-amino-1,3-thiazol-4-yl)-2- {[(1S)-2-{[(3R,5Z)-3-{4-[(2R)-2,3-dihydroxypropyl]- 3-(4,5-dihydroxypyridin-2-yl)-5-oxo-4,5-dihydro- 1H-1,2,4-triazol-1-yl}-3-hydroxy-1,2,3lambda~4~,4- dioxathiazolidin-5-ylidene]amino}-1-formylethyl]amino}- 2-oxoethylidene]amino}oxy)-2-methylpropanoic acid C23 H28 N10 O13 S2 Citation: Structural basis for effectiveness of siderophore-conjugated monocarbams against clinically relevant strains of Pseudomonas aeruginosa. (2010) Proc.Natl.Acad.Sci.USA

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes nosocomial infections for which there are limited treatment options. Penicillin-binding protein PBP3, a key therapeutic target, is an essential enzyme responsible for the final steps of peptidoglycan synthesis and is covalently inactivated by ?-lactam antibiotics. Here we disclose the first high resolution cocrystal structures of the P. aeruginosa PBP3 with both novel and marketed ?-lactams. These structures reveal a conformational rearrangement of Tyr532 and Phe533 and a ligand-induced conformational change of Tyr409 and Arg489. The well-known affinity of the monobactam aztreonam for P. aeruginosa PBP3 is due to a distinct hydrophobic aromatic wall composed of Tyr503, Tyr532, and Phe533 interacting with the gem-dimethyl group. The structure of MC-1, a new siderophore-conjugated monocarbam complexed with PBP3 provides molecular insights for lead optimization. Importantly, we have identified a novel conformation that is distinct to the high-molecular-weight class B PBP subfamily, which is identifiable by common features such as a hydrophobic aromatic wall formed by Tyr503, Tyr532, and Phe533 and the structural flexibility of Tyr409 flanked by two glycine residues. This is also the first example of a siderophore-conjugated triazolone-linked monocarbam complexed with any PBP. Energetic analysis of tightly and loosely held computed hydration sites indicates protein desolvation effects contribute significantly to PBP3 binding, and analysis of hydration site energies allows rank ordering of the second-order acylation rate constants. Taken together, these structural, biochemical, and computational studies provide a molecular basis for recognition of P. aeruginosa PBP3 and open avenues for future design of inhibitors of this class of PBPs.

THERMOLYSIN

Radiation damage study of thermolysin - 160K structure A (0.1 MGy)

Authors:	Juers, D.H.,   Weik, M.
Release Date:	2010-12-08	Classification:	Hydrolase
Experiment:	X-RAY DIFFRACTION with resolution of 2.20 Å
Compound:	1 Polymer Molecule: Thermolysin Polymer: 1 Type: polypeptide(L) Length: 316 Chains: E EC#: 3.4.24.27     Fragment: UNP residues 233-548 2 Ligands Image Identifier Name Formula CA   CALCIUM ION Ca ZN   ZINC ION Zn
Citation:	Not Available.

Molecular description.
Classification: Hydrolase Structure Weight: 34588.30 Molecule: Thermolysin Polymer: 1 Type: polypeptide(L) Length: 316 Chains: E EC#: 3.4.24.27     Fragment: UNP residues 233-548

LEUCYL AMINOPEPTIDASE The zinc-dependent leucine aminopeptidase from Pseudomonas putida (ppLAP) is an important enzyme for the industrial production of enantiomerically pure amino acids. To provide a better understanding of its structure-function relationships, the enzyme was studied by X-ray crystallography. Crystal structures of native ppLAP at pH 9.5 and pH 5.2, and in complex with the inhibitor bestatin, show that the overall folding and hexameric organization of ppLAP are very similar to those of the closely related di-zinc leucine aminopeptidases (LAPs) from bovine lens and Escherichia coli. At pH 9.5, the active site contains two metal ions, one identified as Mn(2+) or Zn(2+) (site 1), and the other as Zn(2+) (site 2). By using a metal-dependent activity assay it was shown that site 1 in heterologously expressed ppLAP is occupied mainly by Mn(2+). Moreover, it was shown that Mn(2+) has a significant activation effect when bound to site 1 of ppLAP. At pH 5.2, the active site of ppLAP is highly disordered and the two metal ions are absent, most probably due to full protonation of one of the metal-interacting residues, Lys267, explaining why ppLAP is inactive at low pH. A structural comparison of the ppLAP-bestatin complex with inhibitor-bound complexes of bovine lens LAP, along with substrate modelling, gave clear and new insights into its substrate specificity and high level of enantioselectivity.

High pH native structure of leucine aminopeptidase from Pseudomonas putida Authors: Kale, A.,   Dijkstra, B.W.,   Sonke, T.,   Thunnissen, A.M.W.H Release Date: 2010-04-14 Classification: Hydrolase    Experiment: X-RAY DIFFRACTION with resolution of 2.20 Å Compound: 1 Polymer  Molecule: Cytosol aminopeptidase Polymer: 1 Type: polypeptide(L) Length: 497 Chains: A, B, C, D, E, F EC#: 3.4.11.1     4 Ligands   Image Identifier Name Formula BCT   BICARBONATE ION C H O3 K   POTASSIUM ION K MN   MANGANESE (II) ION Mn ZN   ZINC ION Zn Citation: Crystal structure of the leucine aminopeptidase from Pseudomonas putida reveals the molecular basis for its enantioselectivity and broad substrate specificity. (2010) J.Mol.Biol. 398: 703-714 PubMed Abstract: The zinc-dependent leucine aminopeptidase from Pseudomonas putida (ppLAP) is an important enzyme for the industrial production of enantiomerically pure amino acids. To provide a better understanding of its structure-function relationships, the enzyme was studied by X-ray crystallography. Crystal structures of native ppLAP at pH 9.5 and pH 5.2, and in complex with the inhibitor bestatin, show that the overall folding and hexameric organization of ppLAP are very similar to those of the closely related di-zinc leucine aminopeptidases (LAPs) from bovine lens and Escherichia coli. At pH 9.5, the active site contains two metal ions, one identified as Mn(2+) or Zn(2+) (site 1), and the other as Zn(2+) (site 2). By using a metal-dependent activity assay it was shown that site 1 in heterologously expressed ppLAP is occupied mainly by Mn(2+). Moreover, it was shown that Mn(2+) has a significant activation effect when bound to site 1 of ppLAP. At pH 5.2, the active site of ppLAP is highly disordered and the two metal ions are absent, most probably due to full protonation of one of the metal-interacting residues, Lys267, explaining why ppLAP is inactive at low pH. A structural comparison of the ppLAP-bestatin complex with inhibitor-bound complexes of bovine lens LAP, along with substrate modelling, gave clear and new insights into its substrate specificity and high level of enantioselectivity. Citation Authors: Kale, A.,   Pijning, T.,   Sonke, T.,   Dijkstra, B.W.,   Thunnissen, A.M.