Richard Nelson Perham. 27 April 1937—14 February 2015 (original) (raw)
Related papers
Crystal Structure of Liganded Rat Peroxisomal Multifunctional Enzyme Type 1
Journal of Biological Chemistry, 2010
The crystal structure of the full-length rat peroxisomal multifunctional enzyme, type 1 (rpMFE1), has been determined at 2.8 Å resolution. This enzyme has three catalytic activities and two active sites. The N-terminal part has the crotonase fold, which builds the active site for the ⌬ 3 ,⌬ 2-enoyl-CoA isomerase and the ⌬ 2-enoyl-CoA hydratase-1 catalytic activities, and the C-terminal part has the (3S)-hydroxyacyl-CoA dehydrogenase fold and makes the (3S)-hydroxyacyl-CoA dehydrogenase active site. rpMFE1 is a multidomain protein having five domains (A-E). The crystal structure of full-length rpMFE1 shows a flexible arrangement of the A-domain with respect to the BE domains. Because of a hinge region near the end of the A-domain, two different positions of the A-domain were observed for the two protein molecules (A and B) of the asymmetric unit. In the most closed conformation, the mode of binding of CoA is stabilized by domains A and B (helix-10), as seen in other crotonase fold members. Domain B, although functionally belonging to the N-terminal part, is found tightly associated with the C-terminal part, i.e. fixed to the E-domain. The two active sites of rpMFE1 are ϳ40 Å apart, separated by a tunnel, characterized by an excess of positively charged side chains. Comparison of the structures of rpMFE1 with the monofunctional crotonase and (3S)-hydroxyacyl-CoA dehydrogenase superfamily enzymes, as well as with the bacterial ␣ 2  2-fatty acid oxidation multienzyme complex, reveals that this tunnel could be important for substrate channeling, as observed earlier on the basis of the kinetics of rpMFE1 purified from rat liver. Multifunctional enzyme, type 1 (MFE1), 2 is one of the most abundant mammalian peroxisomal proteins (1). Its catalytic * This work has been supported by a grant from the Academy of Finland and the Sigrid Juselius Foundation.
Notes of a protein crystallographer: my nights with ACTOR
Acta Crystallographica Section D-biological Crystallography, 2005
It would have appeared to be an impossible dream in the late sixties, when the ®eld of protein crystallography ®rst became established, just as the structures of myoglobin and hemoglobin were ®rst unveiled. Even if somebody would have thought about it in the early seventies, when protein crystallography was`coming of age' (Cold Spring Harbor Symposium, 1971), it would have still seemed utterly impossible or even a miracle. Yet, only 30 years later, here I am late at night putting a protein crystal in front of an extremely brilliant X-ray beam using a computer-controlled robot to mount, center and expose a protein crystal in front of the X-rays emanating from a third-generation synchrotron source. My diffraction data from this crystal will be collected in approximately 15 minutes, processed, as it is being collected, reduced and scaled a few minutes later. Things going well, the three dimensional structures of the protein and various ligand(s) within these crystals will be unveiled tomorrow and presented and discussed with chemists, biologists, pharmacologists rapidly. The detailed analysis will aid and direct the synthesis of new compounds for several drug-design projects. In a year or so, after several iterations of the process, the resulting optimized compound with the most suitable pharmacokinetic properties could be selected for clinical testing. After rigorous clinical studies, it might become one of those rare chemical entities with a therapeutic effect on a speci®c patient population.
Twelfth Enzyme Mechanisms Conference
Bioorganic Chemistry, 1991
at the Catamaran Resort Hotel in San Diego, California. The meetings were organized into sessions on the general topics: (1) Enzyme Mechanisms; (2) Enzyme Structure and Intermediates; (3) Enzyme-Substrate Interactions; (4) Biological Oxidations; and Molecular Recognition. A keynote lecture was delivered on Molecular Studies of the Cyclophilin Class of Isomerases. A poster session was held throughout the meeting, with over 60 posters presented, covering a wide range of mechanistic enzymology. A brief synopsis of each of the major talks is given, including some relevant references to provide an entry into the current work in these areas. A complete listing of the titles and authors of the poster presentations is also included.
The Journal of Physical Chemistry B, 2006
Density functional calculations on horseradish peroxidase mutants are presented, whereby one or two of the nitrogen atoms of the axial histidine ligand have been replaced by phosphorus atoms. Our calculations show that phosphorus entices a push effect on the oxoiron group, whereas a histidine side chain withdraws electrons. As a result, we predict that a phosphorus-substituted histidine ligand will convert the active form of a peroxidase into a monoxygenase. This subsitution may be useful for the bioengineering of commercially exploitable enzymes.
Archives of Biochemistry and Biophysics, 2006
The -oxidation of fatty acids in peroxisomes produces hydrogen peroxide (H 2 O 2) , a toxic metabolite, as a bi-product. Fatty acids -oxidation activity is deWcient in X-linked adrenoleukodystrophy (X-ALD) because of mutation in ALD-gene resulting in loss of very long chain acyl-CoA synthetase (VLCS) activity. It is also aVected in disease with catalase negative peroxisomes as a result of inactivation by H 2 O 2 . Therefore, the following studies were undertaken to delineate the molecular interactions between both the ALD-gene product (adrenoleukodystrophy protein, ALDP) and VLCS as well as H 2 O 2 degrading enzyme catalase and proteins of peroxisomal -oxidation. Studies using a yeast two hybrid system and surface plasmon resonance techniques indicate that ALDP, a peroxisomal membrane protein, physically interacts with VLCS. Loss of these interactions in X-ALD cells may result in a deWciency in VLCS activity. The yeast twohybrid system studies also indicated that catalase physically interacts with L-bifunctional enzyme (L-BFE). Interactions between catalase and L-BFE were further supported by aYnity puriWcation, using a catalase-linked resin. The aYnity bound 74-kDa protein, was identiWed as L-BFE by Western blot with speciWc antibodies and by proteomic analysis. Additional support for their interaction comes from immunoprecipitation of L-BFE with antibodies against catalase as a catalase-L-BFE complex. siRNA for L-BFE decreased the speciWc activity and protein levels of catalase without changing its subcellular distribution. These observations indicate that L-BFE might help in oligomerization and possibly in the localization of catalase at the site of H 2 O 2 production in the peroxisomal -oxidation pathway.
Chemical Reviews, 2004
developed a connection between density functional theory and the theory of broken symmetry, which he and collaborators applied to iron−sulfur clusters and proteins. His current research interests include electron-transfer and protontransfer energetics, reaction pathways in metalloenzymes, optical, Mössbauer, and ENDOR spectroscopy, magnetism in transition metal complexes, photochemistry, and click chemistry. He is interested in fundamental problems including the foundations of density functional theory, the correlation problem, and the uses of the broken symmetry and spin concepts in physics, chemistry, and biology. In his spare time, he and his wife Peggy enjoy playing with their daughter Julia and watching her draw.
Homage to Prof. M.G. Replacement: A Celebration of Structural Biology at Purdue University
Structure, 2005
On a glorious spring day in the American Midwest, friends, colleagues, collaborators, and alumni of Prof. M.G. Replacement gathered together at the campus of Purdue University, West Lafayette, Indiana to celebrate 40 years of structural biology and honor the man behind it all: M.G. Rossmann. The date also corresponded approximately to MGR's 75th birthday. It was a memorable occasion for several reasons. An earlier meeting 10 years ago did also render homage to Michael (New Directions in Protein-Structure Relationships: Symposium in Honor of Professor M.G. Rossmann's 65th Birthday, Purdue University, October 21, 1995), but on this occasion the symposium was much more encompassing of structural biology and had a more global character. A large number of featured speakers presented and discussed advances in vast areas of structural biology and came from the four corners of the world to share their work with the new generations of structural biologists currently being trained at Purdue University.