been refined and analyzed (with Dr. Richard Axel, 
HHMI, Columbia University). Structure determina- 
tions are now in progress for various growth factors, 
including stem cell factor (with Amgen) and ciliary 
neurotrophic factor (with Regeneron). Crystalliza- 
tion efforts continue on extracellular fragments of 
the insulin receptor (with Dr. Joseph Schlessinger, 
New York University) and on other receptors. 
The group also continues its attempts to express 
and crystallize kinases, including proteolytically de- 
fined fragments of the insulin receptor (with Dr. 
Leland Ellis, Texas A&M University, Houston), pro- 
tein kinase C (with Dr. Paul Kirschmeier, Schering- 
Plough), and the lymphocyte kinase p56'''*. In addi- 
tion, x-ray absorption spectroscopy has been used 
(with Dr. Steven Cramer, University of California, 
Davis) to characterize zinc sites in protein kinase C. 
Finally, an initiative on cell adhesion molecules has 
yielded the crystal structure of an adhesive fibronec- 
tin type III domain from tenascin (with Dr. Harold 
Erickson, Duke University) and crystals of a four-do- 
main fibronectin fragment (also with Dr. Erickson) , 
of the myelin sheath adhesin pO (with Dr. David 
Coleman, Columbia University), and of a cadherin 
fragment (also with Dr. Coleman) . 
Replication and Transcription 
Macromolecular interactions involved in the regu- 
lation and catalysis of genetic replication and tran- 
scription are at the heart of molecular biology. The 
Hendrickson group is also involved in studies in this 
area. Following on the previously reported struc- 
ture of ribonuclease H (RNase H) from Escherichia 
coli, inactive site-directed mutants have been pro- 
duced, crystal structures solved, and complexation 
with RNA:DNA hybrids demonstrated. The RNase H 
protein of reverse transcriptase (RT) from Moloney 
murine leukemia virus has been expressed (with Dr. 
Stephen Gofif, Columbia University); a proteolytic 
fragment of the polymerase portion of Moloney RT 
has also been produced (also with Dr. Goff); and 
crystals of the selenomethionyl analogue of the poly- 
merase fragment have been prepared for the struc- 
ture determination. Work has also proceeded on the 
crystallographic analysis of the umuD' mutation- 
repair protein from E. coli (with Dr. Roger Wood- 
gate, National Institutes of Health) and on Taq poly- 
merase (with Dr. David Sharkey, Eastman-Kodak) . 
Carbohydrate Recognition 
The highly glycosylated surfaces of cells help to 
confer a distinctive character, and the identity of 
these carbohydrate labels can be recognized by spe- 
cific animal lectins. A large class of such lectins are 
characterized by calcium-dependent (C-type) car- 
bohydrate recognition domains (CRDs) . Crystals of 
a dimeric CRD fragment from mannose-binding pro- 
tein, an antibody-independent defense agent, have 
been analyzed both as the Ho'^ complex and as a 
Ca^^ complex with a six-mannose glycopeptide 
(with Dr. Kurt Drickamer, Columbia University). 
The structures show that specific binding is dictated 
by direct coordination to a calcium site that involves 
displacement of a water ligand by two sugar hy- 
droxyl groups. Structural work is also proceeding on 
a Fab fragment of antidextran antibody (with Dr. 
Elvin Kabat, Columbia University). 
Other Structural Programs 
Work continues on other problems of long- 
standing interest to this group, including oxygen- 
carrying proteins, metalloproteins, and streptavi- 
din. The copper sites have been located for a 
fragment of octopus hemocyanin (with Dr. Kensal 
van Holde, Oregon State University); structures 
have been refined for streptavidin complexed with 
various biotin analogues; Pyrularia thionin, a rela- 
tive of crambin, has been crystallized (with Dr. 
Leo Vernon, Brigham Young University); and the 
structure determinations for two isoforms of fi- 
bungarotoxin are nearing completion. 
Methodology Development 
Work on methods is an integral aspect of many of 
the structural projects in Dr. Hendrickson's labora- 
tory. The problem of crystallographic phase deter- 
mination remains an important focus of attention, 
and with support from the National Institutes of 
Health, applications of anomalous scattering are be- 
ing explored in this context. 
During the past year a number of extensions have 
been made in methods for multiwavelength anoma- 
lous diffraction (MAD). These include a statistical 
test for enantiomorph selection, improved proce- 
dures for the efficient bacterial incorporation of se- 
lenomethionine into proteins, and the development 
of MAD phasing procedures, with data restricted to 
wavelengths very near absorption edges. The prob- 
lem of refining atomic models into optimal agree- 
ment with diffraction measurements is another ma- 
jor area of interest, and with support from the 
National Science Foundation, procedures are be- 
ing developed for the economical incorpora- 
tion of dynamic information into macromolecular 
refinement. 
A third area of methodology development con- 
cerns crystallographic computing. A convenient 
windowing interface to the many computer pro- 
grams needed in these studies is being developed as 
the Crystallographic Workbench. With support 
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