Active flap

Straub, F.K. Kennedy, D.K. Stemple, A.D. Anand, V.R. Birchette, T.S. Development and Whirl Tower Test of the SMART Active Flap Rotor. Smart Structures and Materials 2004 Industrial and Commercial Applications of Smart Structures Technologies, Eric H. Anderson (Ed.), Proc. SPIE Vol. 5388... 

The HIV-l protease is a remarkable viral imitation of mammalian aspartic proteases It is a dimer of identical subunits that mimics the two-lobed monomeric structure of pepsin and other aspartic proteases. The HIV-l protease subunits are 99-residue polypeptides that are homologous with the individual domains of the monomeric proteases. Structures determined by X-ray diffraction studies reveal that the active site of HIV-l protease is formed at the interface of the homodimer and consists of two aspartate residues, designated Asp and Asp one contributed by each subunit (Figure 16.29). In the homodimer, the active site is covered by two identical flaps, one from each subunit, in contrast to the monomeric aspartic proteases, which possess only a single active-site flap. 

FIGURE 16.29 (left) HIV-1 protease com-plexed with the inhibitor Crixivan (red) made by Merck. The flaps (residues 46-55 from each snbnnit) covering the active site are shown in green and the active site aspartate residues involved in catalysis are shown in white. 

A distinctive feature of the protease is the presence of a mobile beta turn in each subunit, which serves as a flap covering the active site. For substrate to get access to the active site, the flaps have to move away in what must be an ongoing dynamic... 

Fe-TPAA Fe(III)-tris[N-(2-pyridylmethyl)-2-aminoethyl] amine Fe-TPEN Fe(II)-tetrakis-N,N,N, N -(2-pyridyl methyl-2-aminoethyl)amine FFA Free fatty acids FGF Fibroblast growth factor FID Flame ionization detector FITC Fluorescein isothiocyanate FKBP FK506-binding protein FLAP 5-lipoxygenase-activating protein... 

Figure 6.18 Structure of HIV-1 aspartyl protease in the flap open (left panel) and flap closed conformation with an active site-directed inhibitor bound right panel). See color insert.

Poyner RR, Larsen TM, Wong SW, Reed GH (2002) Functional and structural changes due to a serine to alanine mutation in the active-site flap of enolase. Arch Biochem Biophys 401 155—163... 

Figure 2. A ribbon diagram of rhizopus pepsin (PDB code 5APR). The catalytically important Asp dyad (Asp218 and Asp35) side-chains are shown in stick diagrams. The P-hair pin flap that covers the active site cleft is located in the bottom of the diagram.

Leukotrienes (LTA, LTB LTC, LTD, and LTE ) are synthesized from arachi-donic acid by a cascade of enzymes that include 5-lipoxygenase (5-LOX), 5-lipoxy-genase-activating protein (FLAP), and leukotriene C4 synthase (LTC synthase) (79,80). The leukotriene LTA is synthesized by 5-LOX in the first step and is an unstable precursor that is then enzymatically converted to LTB or LTC (80,81), which can subsequently be metabolized to LTD and LTE. LTC, LTD, and LTE are the components of the slow-reacting substance of anaphylaxis. These moieties, particularly LTC and LTD, are active forms of CysLTs that interact with the G protein-coupled cysteinyl leukotriene receptors (CysLtrl and CysLtr2) (70,81,82). Once engaged, the activated CysLtrs receptors stimulate the secretion of mucus and induce edema and bronchoconstriction (81). 

Stereo view of the a-carbon backbone of PR dimer, (a) The apoenzyme with flaps in the open conformation, (b) Inhibited form of HEV PR with flaps in a closed conformation. For clarity, the inhibitor is removed from the active site. 

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