The interface between catalytic and hemopexin domains in matrix metalloproteinase-1 conceals a collagen binding exosite

Matrix metalloproteinase-1 (MMP-1) is an instigator of collagenolysis, the catabolism of triple helical collagen. Previous studies have implicated its hemopexin (HPX) domain in binding and possibly destabilizing the collagen substrate in preparation for hydrolysis of the polypeptide backbone by the catalytic (CAT) domain. Here, we use biophysical methods to study the complex formed between the MMP-1 HPX domain and a synthetic triple helical peptide (THP) that encompasses the MMP-1 cleavage site of the collagen α1(I) chain. The two components interact with 1:1 stoichiometry and micromolar affinity via a binding site within blades 1 and 2 of the four-bladed HPX domain propeller. Subsequent site-directed mutagenesis and assay implicates blade 1 residues Phe(301), Val(319), and Asp(338) in collagen binding. Intriguingly, Phe(301) is partially masked by the CAT domain in the crystal structure of full-length MMP-1 implying that transient separation of the domains is important in collagen recognition. However, mutation of this residue in the intact enzyme disrupts the CAT-HPX interface resulting in a drastic decrease in binding activity. Thus, a balanced equilibrium between these compact and dislocated states may be an essential feature of MMP-1 collagenase activity.     

Alpha-globin gene markers identify genetic differences between Australian aborigines and Melanesians.

Australian aborigines exhibit a number of alpha-globin cluster rearrangements involving both alpha- and zeta-globin genes. alpha+-Thalassemia (-alpha/) in this population is heterogeneous and includes the 3.7 types I, II, and III gene deletions. The alpha alpha alpha/ and zeta zeta zeta/ rearrangements are each found in association with two haplotypes, indicating origins from at least two separate DNA crossover events. Differences in alpha-globin cluster rearrangements and in haplotypes between Australian aborigines, Papua New Guinea highlanders and island Melanesians, are consistent with multiple colonizing events into Australia.     

Composition of triglycerides from aphids of six different families and from different seasonal forms of Aphis evonymi

The triglyceride compositions of extracts and cornicle secretions of specimens from a range of aphid families were examined by mass spectrometry and found to support earlier evidence that there is little correlation between taxonomic position and chemical constitution.

Parasites developing within Myzus persicae preferentially consumed the typical aphid triglycerides which contain hexanoic (C₆), sorbic (C_6:2), myristic (C₁₄), and palmitic (C₁₆) acid moieties, so that when parasitism was advanced, only triglycerides with three long-chain fatty acids per molecule remained. The adult parasites themselves contained very little triglyceride.

Triglycerides of Aphis evonymi and Aphis fabae were similar and varied in composition regularly throughout the year. In the apterous and alate (summer) viviparae, there were equal amounts of myristoyl (C₁₄) and palmitoyl (C₁₆) triglycerides, while in fundatrices and fundatrigeniae (spring forms) myristoyl was predominant. Males collected in autumn resembled the spring forms. However, oviparae and eggs of these and other species differed considerably from the other seasonal forms, in having more hexenoic (C_6:1), sorbic (C_6:2), and myristoleic (C_14:1) acid moieties.     

A Generator-Produced Gallium-68 Radiopharmaceutical for PET Imaging of Myocardial Perfusion

Lipophilic cationic technetium-99m-complexes are widely used for myocardial perfusion imaging (MPI). However, inherent uncertainties in the supply chain of molybdenum-99, the parent isotope required for manufacturing ⁹⁹Mo/^99mTc generators, intensifies the need for discovery of novel MPI agents incorporating alternative radionuclides. Recently, germanium/gallium (Ge/Ga) generators capable of producing high quality ⁶⁸Ga, an isotope with excellent emission characteristics for clinical PET imaging, have emerged. Herein, we report a novel ⁶⁸Ga-complex identified through mechanism-based cell screening that holds promise as a generator-produced radiopharmaceutical for PET MPI.