2v35

Porcine Pancreatic Elastase in complex with inhibitor JM54Porcine Pancreatic Elastase in complex with inhibitor JM54

Structural highlights 2v35 is a 1 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , Related: 1b0e, 1bma, 1btu, 1c1m, 1e34, 1e35, 1e36, 1e37, 1e38, 1eai, 1eas, 1eat, 1eau, 1ela, 1elb, 1elc, 1eld, 1ele, 1elf, 1elg, 1esa, 1esb, 1est, 1fle, 1fzz, 1gvk, 1gwa, 1h9l, 1hax, 1hay, 1haz, 1hb0, 1hv7, 1inc, 1jim, 1l0z, 1l1g, 1lka, 1lkb, 1lvy, 1mcv, 1mmj, 1nes, 1okx, 1qgf, 1qix, 1qnj, 1qr3, 1uo6, 1uvo, 1uvp, 2a7c, 2a7j, 2blo, 2blq, 2cv3, 2d26, 2de8, 2de9, 2est, 2h1u, 2v0b, 3est, 4est, 5est, 6est, 7est, 8est, 9est Activity: Pancreatic elastase, with EC number 3.4.21.36 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CELA1_PIG] Acts upon elastin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The presence of a leaving group at C-4 of monobactams is usually considered to be a requirement for mechanism-based inhibition of human leukocyte elastase by these acylating agents. We report that second-order rate constants for the alkaline hydrolysis and elastase inactivation by N-carbamoyl monobactams are independent of the pKa of the leaving group at C-4. Indeed, the effect exerted by these substituents is purely inductive: electron-withdrawing substituents at C-4 of N-carbamoyl-3,3-diethylmonobactams increase the rate of alkaline hydrolysis and elastase inactivation, with Hammett pI values of 3.4 and 2.5, respectively, which indicate the development of a negative charge in the transition-states. The difference in magnitude between these pI values is consistent with an earlier transition-state for the enzymatic reaction when compared with that for the chemical process. These results suggest that the rate-limiting step in elastase inactivation is the formation of the tetrahedral intermediate, and that beta-lactam ring-opening is not concerted with the departure of a leaving group from C-4. Monobactam sulfones emerged as potent elastase inhibitors even when the ethyl groups at C-3, required for interaction with the primary recognition site, are absent. For one such compound, a 1 : 1 enzyme-inhibitor complex involving porcine pancreatic elastase has been examined by X-ray crystallography and shown to result from serine acylation and sulfinate departure from the beta-lactam C-4. The efficiency of C-4 substituents in activating the beta-lactam scaffold towards serine proteases and hydroxide ion.,Mulchande J, Martins L, Moreira R, Archer M, Oliveira TF, Iley J Org Biomol Chem. 2007 Aug 21;5(16):2617-26. PMID:18019537 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Elastase

spinqualitylabelsall models 2v35, resolution 1.67Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image